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(Circulation. 1999;99:1574-1579.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Influence of Pulmonary Capillary Wedge Pressure on Central Apnea in Heart Failure
From the Departments of Respiratory Medicine and Cardiology, The Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia.
Correspondence to Dr Matthew Naughton, Department of Respiratory Medicine, Alfred Hospital, Commercial Rd, Prahran, Melbourne, Victoria, 3181 Australia. E-mail matthew.naughton{at}med.monash.edu.au
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Abstract |
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Background—Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity.
Methods and Results—Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean±SEM [range]: 22.8±1.2 [11 to 38] versus 12.3±1.2 [4 to 21] versus 11.5±1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0.017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0±2.6 [20 to 38] to 22.0±1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5±7.7 [7 to 62] to 18.5±5.3 [1 to 31] events per hour; P=0.005).
Conclusions—PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.
Key Words: heart failure • sleep • apnea • hemodynamics • hypoxemia
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Introduction |
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Sleep apnea and congestive heart failure (CHF) are common disorders affecting 2% to 4% and 1% of the population, respectively.1 2 Moreover,
40% to 50% of patients
with CHF are reported to have sleep apnea of either nonhypercapnic
central or obstructive types.3 4 Evidence also exists that
recognition and treatment of either form of sleep apnea in patients
with CHF can augment cardiac function.3 5 Central apnea in CHF occurs as a result of ventilatory control instability, and patients typically complain of orthopnea, paroxysmal nocturnal dyspnea, witnessed apneas, fragmented sleep, and excessive daytime sleepiness.6 Recordings of ventilation during sleep reveal a characteristic cyclic pattern of central apnea and hypoxemia followed by crescendo/decrescendo ventilation, associated with an arousal at the peak of ventilation, known classically as Cheyne-Stokes respiration.6
Whereas ventilation is under the influence of several factors during wakefulness, ventilation during non-REM sleep is under a chemical-metabolic control, such that ventilation occurs while the level of metabolic signal (PaCO2) is above the apnea threshold. Instability of this control occurs if (1) the ventilatory response to a given metabolic signal is increased and hyperventilation occurs, (2) oscillations in blood gases with each apnea cannot be buffered (as occurs when the body stores of oxygen or carbon dioxide are diminished or during ventilation/perfusion alterations when the individual is supine and asleep), or (3) the circulatory time between the lungs and chemoreceptors is prolonged.6 Although patients with CHF have circulatory delay, the major abnormality contributing to ventilatory control instability is thought to be hyperventilation and resultant hypocapnia.6 The supranormal ventilatory responses to increasing levels of carbon dioxide and marked hypocapnia observed in CHF patients with central apnea support this hypothesis.6 7
On the basis of animal experiments, it has been proposed that hyperventilation results from elevation of pulmonary interstitial pressure.8 Pulmonary edema and concomitant increase in interstitial pressure stimulates pulmonary J receptors, which lie within the interstitium in close proximity to the pulmonary capillaries.8 Neural impulses are transmitted via afferent pulmonary vagal C fibers to the ventilatory control center in the medulla.9 Stimulation of this afferent vagal system results in brief central apnea followed by tachypnea and hyperventilation.8 9 10
In contrast to central apnea, the pathophysiological abnormality of obstructive apnea is intermittent upper-airway closure against which futile respiratory efforts are made.5 Large negative intrathoracic pressures are generated that increase left ventricular transmural pressure gradient and therefore afterload.11 Moreover, hypoxemia related to apnea and bursts of muscle sympathetic activity related to arousal cause rises in systemic blood pressure that further increase left ventricular afterload.11 However, the adverse effects of obstructive apnea on cardiac function are limited to periods of sleep and may not be apparent during wakefulness.
We hypothesized that the presence of elevated pulmonary vascular pressure in patients with stable CHF would be associated with hypocapnia and central sleep apnea. To test this hypothesis, we compared pressures on the right side of the heart within a group of patients with severe stable CHF, grouped by presence and type of apnea. Second, in the group of patients with central apnea, we assessed the relationship between pulmonary capillary wedge pressure (PCWP) and central apnea frequency and severity. Third, we assessed changes in central apnea frequency after intensive medical therapy in a subgroup of patients with high initial PCWP and central apnea.
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Methods |
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Subjects
Patients being assessed by the Cardiac Transplant Service of the Department of Cardiology at the Alfred Hospital were invited to take part in this study. The Ethics Committee of the Alfred Hospital approved the study, and patients provided written informed consent. Consecutive patients aged 18 to 70 years with clinical evidence of significant chronic CHF and a left ventricular ejection fraction (LVEF) <40% due to ischemic or idiopathic dilated cardiomyopathy were enrolled. All eligible patients participated in the study. All patients were taking medical therapy and were in a stable condition, defined as no hospital admission or medication changes within the preceding 2 weeks. No patient had previously undergone sleep monitoring or treatment for sleep apnea, nor were any patients selected on the basis of possible underlying sleep apnea.
Exclusion criteria included the following: pregnancy; unstable angina; primary valvular, congenital, or restrictive cardiomyopathy; significant renal, neurological, or respiratory disease; and obesity (weight >100 kg). Patients with CHF whose weight is >100 kg do not routinely undergo cardiac transplant assessment because of potential for therapeutic weight loss, donor-matching difficulties, and poor posttransplant outcome related to obesity.12
Sleep Studies
Overnight sleep studies were performed in the usual manner with
a computerized system (Somnostar, SensorMedics Corp); 2
electroencephalogram channels, left and right electro-oculograms, and
submental electromyogram (EMG) were used for the determination of sleep
stages. Sleep stages were manually scored according to standard
criteria by an experienced scorer blinded to the patients'
details.13 Sleep efficiency was defined as total sleep
time divided by time in bed and percent sleep stage as the total time
spent in a particular sleep stage divided by the total sleep time. ECG
and heart rate were recorded continuously from precordial lead
II, arterial oxygen saturation was measured by an ear pulse
oximeter (SpO2), and transcutaneous
PCO2 was measured by a capnograph
placed on the anterior chest wall (Fastrac, SensorMedics Corp). Chest
and abdominal movements were monitored with respiratory effort bands
(Resp-ez, EPM Systems). Oronasal airflow was monitored by thermocouples
(ProTech Services) and snoring was monitored with a piezo snore
sensor (ProTech Services).
A central apnea was defined as an absence of oronasal airflow for 
10
seconds associated with an absence of chest and abdominal movement. A
central hypopnea was defined as a reduction in oronasal airflow
associated with a 2% fall in SpO2
with in-phase chest and abdominal movement, no increase in submental
EMG activity, and absence of snoring. An obstructive apnea was defined
as an absence of oronasal airflow for 10 seconds despite continued
out-of-phase chest and abdominal movements. An obstructive hypopnea was
defined as a reduction in oronasal airflow for 10 seconds associated
with a 2% fall in SpO2 despite
continued out-of-phase chest and abdominal movements, increased
submental EMG activity, or snoring. A mixed apnea was defined as
absence of oronasal airflow associated with central followed by
obstructive components. Because upper-airway closure occurs during
mixed apneas, as a result of upper-airway instability, these events
were defaulted into the obstructive sleep apnea group. The
apnea-hypopnea index is the total number of apneas and hypopneas
divided by the total sleep time and is expressed as the number of
events per hour.
Awake Measurements
Catheterization of the right side of the heart
was performed in the morning, while subjects were awake, and was
followed by a sleep study that night. All procedures were performed by
experienced cardiologists involved in the study but blinded to the
sleep study results. Pressure measurements were recorded on the
right side of the heart by use of a balloon-tipped flotation
thermodilution catheter (7F Arrow, Arrow International) via the right
internal jugular vein while subjects were in the supine position.
Cardiac output was measured by the thermodilution technique at the
pulmonary artery position, and an average was calculated from 3
values that varied by <10%. Cardiac index was calculated as cardiac
output divided by body surface area. Transpulmonary gradient
was calculated as the difference between mean pulmonary artery
pressure (PAP) and PCWP. Pulmonary vascular resistance was
calculated as the transpulmonary gradient divided by cardiac
output. Arterial blood gas samples were drawn 1 hour before
sleep onset, while subjects were supine but awake, after 10 minutes
of undisturbed rest. Awake LVEF was measured by
99mTc radionuclide angiography by the
equilibrium method and was also accomplished within the assessment
period.
Protocol
Each patient underwent complete assessment over a 3-day period.
On the basis of the results of the sleep study, patients were divided
into 3 groups depending on the presence and type of sleep apnea, with a
cutoff apnea-hypopnea index >5 events per hour. Patients were
classified as having central apnea if 85% of their events were
purely central in origin. All others with an apnea-hypopnea index >5
were classified as having obstructive apnea, including those with mixed
apneas. Patients with elevated PCWP and central apnea were invited to
undergo repeat investigation after intensive medical therapy.
Statistical Analysis
Right-heart catheter data were compared between the 3 groups by
1-way ANOVA with Tukey post hoc analysis. PCWP was correlated
with awake PaCO2 and indexes of
central apnea frequency (apnea-hypopnea index) and severity (minimum
sleep SpO2 and percent of total sleep
time spent with SpO2 <90%) within
the central apnea group by Pearson least squares method of
analysis. Data are expressed as mean±SEM. A P value
of <0.05 was regarded as significant.
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Results |
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Subject Characteristics
Seventy-five patients (61 men, 14 women) were studied, of whom 53 had sleep apnea (71%) (Table 1
).
Thirty-three patients (44% of the patient population) had central
apnea, and 20 (27%) had obstructive apnea. The incidence of central
and obstructive apnea, respectively, was 42% and 17% for an
apnea-hypopnea threshold of 10 events per hour, 32% and 11% for an
apnea-hypopnea threshold of 15 events per hour, and 24% and 9% for an
apnea-hypopnea threshold of 20 events per hour.
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Age, body mass index, LVEF, and lung function were not significantly
different between the 3 groups (Table 1
). The central apnea
group had a significantly higher pH and lower
PaCO2, with similar
PaO2 and
SaO2, compared with both the
obstructive apnea and the nonapnea groups. The medications used in each
group were similar.
Sleep Data
There were no significant differences in sleep architecture
between groups except that the central apnea group had significantly
less stage 3 and stage 4 sleep and more frequent arousals than the
nonapnea group (Table 2). The central
apnea group also had significantly lower minimum
SpO2 and greater total sleep time
spent with SpO2 <90% than did the
nonapnea group. Although overnight transcutaneous
PCO2 could be measured in only 42 of
75 subjects studied, there was a trend for lower transcutaneous
PCO2 during sleep within the central
apnea group compared with the obstructive apnea and nonapnea
groups, but the difference failed to reach statistical
significance (38.4±0.7 versus 42.2±1.4 versus 40.4±0.8 mm Hg,
respectively; P=0.11).
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Right-Heart Catheter Data
PCWP and mean PAP were markedly higher in the central apnea group
than in the obstructive apnea and nonapnea groups (Table 3). PCWP (in mm Hg; mean±SEM
[range]) in the central apnea group was significantly greater
(22.8±1.2 [11 to 38]) than in the obstructive apnea group (12.3±1.2
[4 to 21]) or the nonapnea group (11.5±1.5 [3 to 28])
(P<0.001). There were no significant differences in PCWP or
PAP between the obstructive apnea and nonapnea groups.
Pulmonary vascular resistance, cardiac index, and
transpulmonary gradient were not significantly different
between the 3 groups.
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Within the central apnea group, PCWP correlated significantly with
PaCO2 (r=-0.42,
P=0.017) and indexes of central apnea frequency and
severity, namely, apnea-hypopnea index (r=0.47,
P=0.006) (Figure 1), total
sleep time with SpO2 <90%
(r=0.51, P=0.002), and minimum sleep
SpO2 (r=-0.36,
P=0.049).
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Seven patients with elevated PCWP and central apnea underwent repeat
investigations after a period of intensive tailored medical therapy
(3.6±0.8 months; range, 1 to 6 months) comprising increased
diuretics (n=6) and/or ACE inhibition (n=4) or the introduction
of nitrates (n=2), carvedilol (n=2), or continuous positive airway
pressure (CPAP) (n=3). The patients undergoing CPAP therapy were
restudied without CPAP. In all 7 subjects, there was a fall in both
PCWP (29.0±2.6 [20 to 38] to 22.0±1.8 [17 to 27] mm Hg;
P<0.001) and central apnea frequency (38.5±7.7 [7 to 62]
to 18.5±5.3 [1 to 31] events per hour; P=0.005) (Figure 2).
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Discussion |
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A number of novel findings emerge from this study, which was conducted within a group of patients with severe stable CHF who were being assessed for cardiac transplant. We have shown that PCWP in patients with central apnea is approximately double that observed in nonapnea and obstructive apnea patients. A significant correlation existed between PCWP and central apnea frequency and severity in the central apnea group. After intensive medical therapy, a fall in PCWP was associated with a fall in central apnea frequency. Together, this provides strong evidence of a highly significant relationship between PCWP and the degree of central apnea.
Although the central apnea group had a significantly greater PCWP than either the nonapnea or the obstructive apnea group, cardiac index and LVEF were not significantly different between the 3 groups, which suggests a primary defect of central control of ventilation rather than of cardiac function in patients with central apnea. When an apnea-hypopnea threshold of 20 events per hour was used, which is generally regarded as a level of significant sleep apnea that requires treatment, central apnea occurred in 24% and obstructive apnea in 9% of patients being evaluated for cardiac transplant assessment, for an overall apnea prevalence of 33%.3
Central sleep apnea is precipitated by hyperventilation that results in the PaCO2 level falling below the apneic threshold during non-REM sleep.6 During the apnea, the PaCO2 level rises, and once above the apnea threshold, hyperventilation resumes. This further propagates hypocapnia, again causing central apnea, giving a classic Cheyne-Stokes pattern of respiration. Based on animal experimentation, it is likely that pulmonary venous congestion and elevation of interstitial pressure cause increased pulmonary vagal afferent nerve stimulation, which precipitates central apnea followed by rapid shallow ventilation with an increased minute ventilation.9 10 These mechanistic observations, however, are limited to surgically instrumented animal models, studied under anesthesia, with experimentally induced pulmonary edema over a few hours rather than over months to years, as experienced by humans with CHF. Moreover, the effect of elevated pulmonary vascular filling pressures on PaCO2 levels or cyclical central apnea was not studied. Given the limitations of animal experiments, the current data support the hypothesis of increased vagal nerve activity with pulmonary edema related to CHF.
Considerable evidence supports the concept that the extent of central apnea is dependent on the degree of hyperventilation and hypocapnia. Central apneas induced by exposure of normal subjects to hypoxic gas mixtures were abolished by inhalation of CO2.14 In patients with CHF, the evidence suggesting dependence of central apnea on hyperventilation and hypocapnia is 5-fold. First, patients with CHF and central apnea have significantly lower PCO2 levels, awake and asleep, than LVEF-matched nonapnea patients.6 Second, in CHF patients, periods of central apnea are associated with significantly greater minute ventilation and lower PCO2 than during nonapnea periods.6 Third, cycles of central apneas during sleep are triggered by a large breath and a concomitant fall in PCO2.6 Fourth, the severity of central apnea is inversely proportional to the overnight PCO2.6 Finally, attenuation of central apnea with a 4-week course of nightly CPAP is associated with a fall in arousal frequency, a reduction in minute ventilation, and a rise in PCO2 during sleep, an effect associated with improved cardiac function.15
The data from the current study, which suggest that PCWP is inversely proportional to PaCO2 levels and directly proportional to the degree of central apnea, are therefore consistent with basic experimental data from animals and other observational data from humans. It also suggests that mechanisms relating pulmonary edema to hyperventilation observed in animals may well pertain to humans.
The obstructive apnea group had awake pulmonary vascular pressures similar to the nonapnea group and lower than those patients with central apnea. It must be emphasized that the obstructive apnea group did not have the "obesity-hypoventilation syndrome" with secondary pulmonary hypertension. In a recent study, such patients were described as markedly obese (mean body mass index 34 kg/m2), relatively hypoxemic when awake (mean PaO2 64 mm Hg), severely hypoxemic when asleep (mean sleep SpO2 76%), and had a mean PAP of 26.0 mm Hg and resting PCWP of 8.3 mm Hg.16 In contrast, the patients with obstructive apnea and CHF in the present study were less obese (mean body mass index 27.9 kg/m2), and less hypoxemic awake (mean PaO2 82.8 mm Hg) and asleep (mean SpO2=93%) yet had similar mean PAP (20.4 mm Hg) and slightly greater PCWP values (mean 12.3 mm Hg). Pulmonary vascular pressures in the obstructive apnea group are likely to increase during sleep. In a study of moderately obese patients (mean weight 113 kg) with obstructive sleep apnea, both PAP and PCWP rose significantly from wakefulness to sleep (20 to 32 mm Hg and 12 to 20 mm Hg, respectively), which suggests adverse effects of hypoxia and negative intrathoracic pressures on pulmonary vascular pressures.17 The current study emphasizes that it is important to recognize that significant obstructive apnea may occur in CHF in the absence of marked awake hypoxemia or obesity.
This study highlights the relative frequency of sleep apnea in patients
with stable CHF and extends the observation of sleep apnea in 45% of
42 patients with stable CHF reported by Javaheri et al.4
Several distinctions need to be made between our studies. First,
Javaheri et al did not report the relative frequency of central or
obstructive apnea in their patient population, nor were detailed
concurrent measurements of cardiac function made. Second, Javaheri et
al defined sleep apnea using an apnea-hypopnea index of 20 events per
hour. If a similar apnea-hypopnea threshold were applied to the current
study, then 33% of the sample (24% patients with central apnea and
9% with obstructive apnea) would be classified as having sleep apnea.
This apparent difference in sleep apnea prevalence in patients with
stable CHF could be explained by the fact that the patients reported by
Javaheri et al were older, were all male, and were more
obese.
Recognition of patients with elevated pulmonary vascular pressures may alert clinicians that such patients may have central sleep apnea. This is important because previous studies of CHF patients have suggested a greater mortality in those with elevated pulmonary vascular pressures and elevated levels of sympathetic activity.18 More recent studies19 20 have shown that CHF patients with central apnea have elevated levels of awake plasma norepinephrine and overnight urinary catecholamines and possibly a greater mortality rate than nonapnea CHF patients matched for LVEF. The observations of the present study complement the above predictors of CHF mortality. Moreover, new therapies that attenuate central apnea, namely, CPAP, oxygen, theophylline, or more intensive pharmacological therapy, have in recent times shown promise as adjunctive therapy for CHF.3 21 22 23
In summary, elevated PCWP in patients with severe yet stable CHF is associated with hypocapnia and central apnea. This observation is consistent with experimental data from animals that indicate that increased pulmonary vagal afferent nerve traffic secondary to pulmonary edema stimulates hyperventilation and hypocapnia. Compared with CHF patients with obstructive apnea or no apnea, patients with central apnea have greater PCWP and PAP and are therefore likely to have more severe heart failure and possibly a worse prognosis. Finally, given the 33% prevalence of clinically significant sleep apnea in patients with stable CHF, recognition and specific treatment of such patients may improve their grave prognosis.
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Acknowledgments |
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Dr Solin is the recipient of an Australian National Health and Medical Research Council Scholarship. Dr Naughton is the recipient of an Australian Lung Foundation/Astra Career Development Award and a Viertal Clinical Investigatorship. The authors would like to acknowledge Associate Professor Tony Dart and Professor Garry Jennings in assisting with catheter studies, and the technical assistance of Sue Tamblyn, Wendy Moule, Teanau Roebuck, Leonie Johnson, and the staff of the sleep, respiratory function, and cardiac catheter laboratories.
Received August 12, 1998; revision received December 1, 1998; accepted December 17, 1998.
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 D. Yumino and T. D. Bradley Central Sleep Apnea and Cheyne-Stokes Respiration Proceedings of the ATS, February 15, 2008; 5(2): 226 - 236. [Abstract] [Full Text] [PDF]
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L. J. Olson, A. M. Arruda-Olson, V. K. Somers, C. G. Scott, and B. D. Johnson Exercise Oscillatory Ventilation: Instability of Breathing Control Associated With Advanced Heart Failure Chest, February 1, 2008; 133(2): 474 - 481. [Abstract] [Full Text] [PDF]
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P. Agostoni, A. Apostolo, and R. K. Albert Mechanisms of Periodic Breathing During Exercise in Patients With Chronic Heart Failure Chest, January 1, 2008; 133(1): 197 - 203. [Abstract] [Full Text] [PDF]
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 S. Javaheri Treatment of obstructive and central sleep apnoea in heart failure: practical options Eur. Respir. Rev., December 1, 2007; 16(106): 183 - 188. [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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M. L. Stanchina, K. Ellison, A. Malhotra, M. Anderson, M. Kirk, M. E. Benser, C. Tosi, C. Carlisle, R. P. Millman, and A. Buxton The Impact of Cardiac Resynchronization Therapy on Obstructive Sleep Apnea in Heart Failure Patients: A Pilot Study Chest, August 1, 2007; 132(2): 433 - 439. [Abstract] [Full Text] [PDF]
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L. J. Olson and V. K. Somers Treating Central Sleep Apnea in Heart Failure: Outcomes Revisited Circulation, June 26, 2007; 115(25): 3140 - 3142. [Full Text] [PDF]
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M. Arzt, J. S. Floras, A. G. Logan, R. J. Kimoff, F. Series, D. Morrison, K. Ferguson, I. Belenkie, M. Pfeifer, J. Fleetham, et al. Suppression of Central Sleep Apnea by Continuous Positive Airway Pressure and Transplant-Free Survival in Heart Failure: A Post Hoc Analysis of the Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure Trial (CANPAP) Circulation, June 26, 2007; 115(25): 3173 - 3180. [Abstract] [Full Text] [PDF]
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A. Noda, H. Izawa, H. Asano, S. Nakata, A. Hirashiki, Y. Murase, S. Iino, K. Nagata, T. Murohara, Y. Koike, et al. Beneficial Effect of Bilevel Positive Airway Pressure on Left Ventricular Function in Ambulatory Patients With Idiopathic Dilated Cardiomyopathy and Central Sleep Apnea-Hypopnea: A Preliminary Study Chest, June 1, 2007; 131(6): 1694 - 1701. [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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O. Oldenburg, B. Lamp, L. Faber, H. Teschler, D. Horstkotte, and V. Topfer Sleep-disordered breathing in patients with symptomatic heart failure A contemporary study of prevalence in and characteristics of 700 patients Eur J Heart Fail, March 1, 2007; 9(3): 251 - 257. [Abstract] [Full Text] [PDF]
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 B. J. Chenuel, C. A. Smith, J. B. Skatrud, K. S. Henderson, and J. A. Dempsey Increased propensity for apnea in response to acute elevations in left atrial pressure during sleep in the dog J Appl Physiol, July 1, 2006; 101(1): 76 - 83. [Abstract] [Full Text] [PDF]
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 M. Arzt and T. D. Bradley Treatment of Sleep Apnea in Heart Failure Am. J. Respir. Crit. Care Med., June 15, 2006; 173(12): 1300 - 1308. [Abstract] [Full Text] [PDF]
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S. Ferreira, J. Winck, P. Bettencourt, and F. Rocha-Goncalves Heart failure and sleep apnoea: To sleep perchance to dream Eur J Heart Fail, May 1, 2006; 8(3): 227 - 236. [Abstract] [Full Text] [PDF]
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S. Javaheri Acetazolamide Improves Central Sleep Apnea in Heart Failure: A Double-Blind, Prospective Study Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 234 - 237. [Abstract] [Full Text] [PDF]
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U. Corra, M. Pistono, A. Mezzani, A. Braghiroli, A. Giordano, P. Lanfranchi, E. Bosimini, M. Gnemmi, and P. Giannuzzi Sleep and Exertional Periodic Breathing in Chronic Heart Failure: Prognostic Importance and Interdependence Circulation, January 3, 2006; 113(1): 44 - 50. [Abstract] [Full Text] [PDF]
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S. M. Caples, R. Wolk, and V. K. Somers Influence of cardiac function and failure on sleep-disordered breathing: evidence for a causative role J Appl Physiol, December 1, 2005; 99(6): 2433 - 2439. [Abstract] [Full Text] [PDF]
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 L J Cormican and A Williams Sleep disordered breathing and its treatment in congestive heart failure Heart, October 1, 2005; 91(10): 1265 - 1270. [Abstract] [Full Text] [PDF]
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 J. Y. Gabor, D. A. Newman, V. Barnard-Roberts, V. Korley, I. Mangat, P. Dorian, and P. J. Hanly Improvement in Cheyne-Stokes respiration following cardiac resynchronisation therapy Eur. Respir. J., July 1, 2005; 26(1): 95 - 100. [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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C. Nopmaneejumruslers, Y. Kaneko, V. Hajek, V. Zivanovic, and T. D. Bradley Cheyne-Stokes Respiration in Stroke: Relationship to Hypocapnia and Occult Cardiac Dysfunction Am. J. Respir. Crit. Care Med., May 1, 2005; 171(9): 1048 - 1052. [Abstract] [Full Text] [PDF]
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M. Arzt, M. Schulz, R. Wensel, S. Montalvan, F. C. Blumberg, G. A. J. Riegger, and M. Pfeifer Nocturnal Continuous Positive Airway Pressure Improves Ventilatory Efficiency During Exercise in Patients With Chronic Heart Failure Chest, March 1, 2005; 127(3): 794 - 802. [Abstract] [Full Text] [PDF]
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 J. A Dempsey, C. A Smith, T. Przybylowski, B. Chenuel, A. Xie, H. Nakayama, and J. B Skatrud The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep J. Physiol., October 1, 2004; 560(1): 1 - 11. [Abstract] [Full Text] [PDF]
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E. Quintana-Gallego, M. Villa-Gil, C. Carmona-Bernal, G. Botebol-Benhamou, A. Martinez-Martinez, A. Sanchez-Armengol, J. Polo-Padillo, and F. Capote Home respiratory polygraphy for diagnosis of sleep-disordered breathing in heart failure Eur. Respir. J., September 1, 2004; 24(3): 443 - 448. [Abstract] [Full Text] [PDF]
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H.F. Becker Bigger numbers needed! Eur. Respir. J., May 1, 2004; 23(5): 659 - 660. [Full Text] [PDF]
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T. Roebuck, P. Solin, D.M. Kaye, P. Bergin, M. Bailey, and M.T. Naughton Increased long-term mortality in heart failure due to sleep apnoea is not yet proven Eur. Respir. J., May 1, 2004; 23(5): 735 - 740. [Abstract] [Full Text] [PDF]
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B. K. Gehlbach and E. Geppert The Pulmonary Manifestations of Left Heart Failure Chest, February 1, 2004; 125(2): 669 - 682. [Abstract] [Full Text] [PDF]
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D. R. Mansfield, N. C. Gollogly, D. M. Kaye, M. Richardson, P. Bergin, and M. T. Naughton Controlled Trial of Continuous Positive Airway Pressure in Obstructive Sleep Apnea and Heart Failure Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 361 - 366. [Abstract] [Full Text] [PDF]
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D. R. Mansfield, P. Solin, T. Roebuck, P. Bergin, D. M. Kaye, and M. T. Naughton The Effect of Successful Heart Transplant Treatment of Heart Failure on Central Sleep Apnea Chest, November 1, 2003; 124(5): 1675 - 1681. [Abstract] [Full Text] [PDF]
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M. Hayashi, K. Fujimoto, K. Urushibata, S.-i. Uchikawa, H. Imamura, and K. Kubo Nocturnal Oxygen Desaturation Correlates With the Severity of Coronary Atherosclerosis in Coronary Artery Disease Chest, September 1, 2003; 124(3): 936 - 941. [Abstract] [Full Text] [PDF]
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J. J. Leite, A. J. Mansur, H. F. G. de Freitas, P. R. Chizola, E. A. Bocchi, M. Terra-Filho, J. A. Neder, and G. Lorenzi-Filho Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2175 - 2181. [Abstract] [Full Text] [PDF]
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T. D. Bradley The ups and downs of periodic breathing: Implications for mortality in heart failure J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2182 - 2184. [Full Text] [PDF]
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R. S. T. Leung, J. S. Floras, G. Lorenzi-Filho, F. Rankin, P. Picton, and T. D. Bradley Influence of Cheyne-Stokes Respiration on Cardiovascular Oscillations in Heart Failure Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1534 - 1539. [Abstract] [Full Text] [PDF]
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R. N. Khayat, A. Xie, A. K. Patel, A. Kaminski, and J. B. Skatrud Cardiorespiratory Effects of Added Dead Space in Patients With Heart Failure and Central Sleep Apnea Chest, May 1, 2003; 123(5): 1551 - 1560. [Abstract] [Full Text] [PDF]
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M. Arzt, M. Harth, A. Luchner, F. Muders, S. R. Holmer, F. C. Blumberg, G. A.J. Riegger, and M. Pfeifer Enhanced Ventilatory Response to Exercise in Patients With Chronic Heart Failure and Central Sleep Apnea Circulation, April 22, 2003; 107(15): 1998 - 2003. [Abstract] [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. Solin, D. M. Kaye, P. J. Little, P. Bergin, M. Richardson, and M. T. Naughton Impact of Sleep Apnea on Sympathetic Nervous System Activity in Heart Failure Chest, April 1, 2003; 123(4): 1119 - 1126. [Abstract] [Full Text] [PDF]
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D. Mansfield, D. M. Kaye, H. Brunner La Rocca, P. Solin, M. D. Esler, and M. T. Naughton Raised Sympathetic Nerve Activity in Heart Failure and Central Sleep Apnea Is Due to Heart Failure Severity Circulation, March 18, 2003; 107(10): 1396 - 1400. [Abstract] [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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P. Solin, D.M. Jackson, T. Roebuck, and M.T. Naughton Cardiac diastolic function and hypercapnic ventilatory responses in central sleep apnoea Eur. Respir. J., September 1, 2002; 20(3): 717 - 723. [Abstract] [Full Text] [PDF]
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A. A. El-Solh, E. Bozkanat, J. Mador, and B. J. B. Grant Association Between Plasma Endothelin-1 Levels and Cheyne-Stokes Respiration in Patients With Congestive Heart Failure* Chest, June 1, 2002; 121(6): 1928 - 1934. [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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T. D. Bradley Crossing the Threshold: Implications for Central Sleep Apnea Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1203 - 1204. [Full Text] [PDF]
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A. Xie, J. B. Skatrud, D. S. Puleo, P. S. Rahko, and J. A. Dempsey Apnea-Hypopnea Threshold for CO2 in Patients with Congestive Heart Failure Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1245 - 1250. [Abstract] [Full Text] [PDF]
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H. Nakayama, C. A. Smith, J. R. Rodman, J. B. Skatrud, and J. A. Dempsey Effect of Ventilatory Drive on Carbon Dioxide Sensitivity below Eupnea during Sleep Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1251 - 1260. [Abstract] [Full Text] [PDF]
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G. Lorenzi-Filho, E.R. Azevedo, J.D. Parker, and T.D. Bradley Relationship of carbon dioxide tension in arterial blood to pulmonary wedge pressure in heart failure Eur. Respir. J., January 1, 2002; 19(1): 37 - 40. [Abstract] [Full Text] [PDF]
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 R. Shabetai Depression and Heart Failure Psychosom Med, January 1, 2002; 64(1): 13 - 14. [Full Text] [PDF]
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R. S. T. LEUNG and T. DOUGLAS BRADLEY Sleep Apnea and Cardiovascular Disease Am. J. Respir. Crit. Care Med., December 15, 2001; 164(12): 2147 - 2165. [Full Text] [PDF]
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A. T. Yan, T. D. Bradley, and P. P. Liu The Role of Continuous Positive Airway Pressure in the Treatment of Congestive Heart Failure Chest, November 1, 2001; 120(5): 1675 - 1685. [Abstract] [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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R. Tkacova, M. Niroumand, G. Lorenzi-Filho, and T. D. Bradley Overnight Shift From Obstructive to Central Apneas in Patients With Heart Failure : Role of PCO2 and Circulatory Delay Circulation, January 16, 2001; 103(2): 238 - 243. [Abstract] [Full Text] [PDF]
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P. SOLIN, T. ROEBUCK, D. P. JOHNS, E. HAYDN WALTERS, and M. T. NAUGHTON Peripheral and Central Ventilatory Responses in Central Sleep Apnea with and without Congestive Heart Failure Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2194 - 2200. [Abstract] [Full Text]
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D. D. Sin, A. G. Logan, F. S. Fitzgerald, P. P. Liu, and T. D. Bradley Effects of Continuous Positive Airway Pressure on Cardiovascular Outcomes in Heart Failure Patients With and Without Cheyne-Stokes Respiration Circulation, July 4, 2000; 102(1): 61 - 66. [Abstract] [Full Text] [PDF]
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 I. Wilcox, S. G. McNamara, C. E. Sullivan, D. D. Sin, G. C. Man, R. L. Jones, and S. Javaheri Central Sleep Apnea and Heart Failure N. Engl. J. Med., January 27, 2000; 342(4): 293 - 294. [Full Text]
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D. D. SIN, F. FITZGERALD, J. D. PARKER, G. NEWTON, J. S. FLORAS, and T. D. BRADLEY Risk Factors for Central and Obstructive Sleep Apnea in 450 Men And Women with Congestive Heart Failure Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1101 - 1106. [Abstract] [Full Text]
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