(Circulation. 1999;100:2418.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Oscillatory Breathing Patterns During Wakefulness in Patients With Chronic Heart Failure
Clinical Implications and Role of Augmented Peripheral Chemosensitivity
From Cardiac Medicine (P.P., S.D.A., T.P.C., D.F., P.A.P.-W., A.J.S.C., M.P.), Imperial College, National Heart & Lung Institute, London, UK; the Cardiology Department (P.P., W.B.), Clinical Military Hospital, Wroclaw, Poland; and Franz-Volhard-Klinik (S.D.A.), Charité, Campus Berlin-Buch, at Max-Delbrück-Centrum, Berlin, Germany.
Correspondence to Piotr Ponikowski, MD, PhD, Cardiac Medicine, National Heart & Lung Institute, Dovehouse St, London SW3 6LY, UK.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Oscillatory breathing patterns characterized by rises and falls in ventilation with apnea (Cheyne-Stokes respiration [CSR]) or without apnea (periodic breathing [PB]) commonly occur during the daytime in chronic heart failure (CHF). We have prospectively characterized patients with cyclical breathing in terms of clinical characteristics, indices of autonomic control, prognosis, and the role of peripheral chemosensitivity.
Methods and Results—To determine cyclical breathing pattern, power spectral analysis was applied to 30-minute recordings of respiration in 74 stable CHF patients. Analyses of heart rate variability and baroreflex sensitivity were used to assess autonomic balance. Peripheral chemosensitivity was assessed with the transient hypoxia method. We also determined whether the suppression of peripheral chemoreceptor activity (hyperoxia or dihydrocodeine) would influence the respiratory pattern. Cyclical respiration was found in 49 (66%) patients (22 [30%] CSR, 27 [36%] PB) and was associated with more advanced CHF symptoms, impaired autonomic balance, and increased chemosensitivity (0.80 and 0.75 versus 0.34 L · min-1 · %SaO2-1, P<0.001, for CSR and PB versus normal breathing, respectively). Transient hyperoxia abolished oscillatory breathing in 7 of 8 patients. Dihydrocodeine administration decreased chemosensitivity by 42% (P=0.05), which correlated with improvement in respiratory pattern. Cyclical breathing predicted poor 2-year survival (relative risk 9.41, P<0.01, by Cox proportional hazards analysis), independent of peak oxygen consumption (P=0.04).
Conclusions—An oscillatory breathing pattern during the daytime is a marker of impaired autonomic regulation and poor outcome. Augmented activity of peripheral chemoreceptors may be involved in the genesis of this respiratory pattern. Modulation of peripheral chemosensitivity can reduce or abolish abnormal respiratory patterns and may be an option in the management of CHF patients with oscillatory breathing.
Key Words: respiration • heart failure • receptors
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Cheyne-Stokes respiration (CSR) during sleep is common in chronic heart failure (CHF).1 The episodes of apnea with concomitant hypoxemia and arousal, which are characteristic features of CSR, may be associated with increased sympathetic activity and precipitate ventricular arrhythmias.2 3 A similar pattern of respiration during the daytime has been recently related to a poor outcome.4 Patients with compensated CHF also demonstrate an oscillatory breathing pattern characterized by cyclical rises and falls in ventilation without true periods of apnea (periodic breathing [PB]).5 6 The physiological basis and clinical importance of such breathing disorders in awake CHF patients have not been clearly established.
Augmented peripheral chemoreceptor activity in CHF may produce in some patients the expression of slow rhythms in heart rate.7 These oscillations in heart rate often coincide with similar rhythms in respiration.6 7 Increased peripheral chemoreceptor activity may result in an instability of cardiorespiratory control, which when coupled with impaired baroreflex sensitivity can lead to slow oscillations in blood pressure and respiration.8 9 Therefore, it is plausible to speculate on the role of peripheral chemoreceptor overactivity in the genesis of cyclical respiration in CHF.
The aim of the present study was to detect the prevalence and characteristics of patients with a cyclical breathing pattern (PB or CSR) during the daytime, in terms of clinical CHF severity and indices of autonomic balance. We have evaluated the role of peripheral chemosensitivity and the effects of its suppression in the genesis of PB/CSR.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
All consecutive patients who attended our outpatient CHF clinic between August 1994 and June 1996 and met the following criteria were considered as candidates for the study: >6-month history of CHF due to idiopathic dilated cardiomyopathy or ischemic heart disease, clinical stability for >1 month, sinus rhythm, no signs of fluid retention, unchanged medication, and no acute coronary event within 6 months preceding the study. Exclusion criteria included pulmonary disease, significant renal dysfunction, diabetes mellitus, autonomic neuropathy, and treatment with ß-blockers. The study protocol was approved by the local ethics committee.
Assessment of PB
Patients were studied in the morning (9 to 12 AM)
and were asked not to smoke or drink caffeine on the study day. After a
20-minute period of supine rest in a quiet room, 30-minute
recordings of a respiratory signal (mercury-in-silastic
strain-gauge plethysmograph, Hokanson) were obtained. A strain gauge
was positioned over the lower part of the chest to obtain a clear
respiratory signal, visually checked, and adjusted according to the
scale of the plethysmograph. The equipment was calibrated
electronically before each test.7 8 Subjects breathed
spontaneously and were asked to relax but not to fall asleep during
tests. By this method, the volume changes of the rib cage were
monitored, and the output signal reflected changes in lung volume.
Continuous recordings of heart rate (ECG) and noninvasive blood
pressure (Finapres, Ohmeda) signals were performed.7 8
Stationary 20-minute recordings were selected, and to identify
oscillatory respiratory patterns producing an amplitude modulation in
the breathing signal, autoregressive power spectral analysis
was applied to the respiratory time series with 15 as a model order.
After power decomposition, the very-low-frequency (VLF) band (from
0.003 to 0.04 Hz) was identified. The occurrence of a discrete
well-defined peak in the VLF band, >5% of total variability, was
considered as evidence of a cyclical breathing pattern. PB was defined
as a pattern of waxing and waning of ventilation without periods of
apnea, and when periodic apnea was detected, this was classified as
CSR.6 In every case of the presence of PB/CSR, the central
frequency (Hz) of the VLF respiratory component was calculated to
obtain the PB or CSR cycle length (seconds). Figures 1
and 2
present examples of CSR and PB, respectively.
|
|
Evaluation of Autonomic Balance
Stationary 20-minute periods of recording were selected,
and autoregressive power spectral analysis was applied to the
R-R interval and systolic blood pressure time
series.7 8 The following spectral bands were identified:
VLF, low frequency (LF, from 0.04 to 0.15 Hz), and high frequency (HF,
from 0.15 to 0.40 Hz). Total power (TP, from 0 to 0.50 Hz) and the
areas below each peak were calculated in absolute units
(ms2) or as normalized units (nu, with VLF
[%TP] as the percentage of TP and LF [nu], and HF [nu] as the
percentages of the TP within the LF and HF bands, respectively, after
the subtraction of the VLF component). Cross-spectral analysis
was used to assess the relation between oscillations in
respiration and R-R interval and systolic blood pressure within
the VLF band.10 Baroreflex sensitivity was assessed by the
phenylephrine method.8
Peripheral Chemosensitivity Evaluation
Peripheral chemosensitivity was assessed using the
transient hypoxia method.11 Minute ventilation was
measured breath by breath, and continuous monitoring of
O2 and CO2 concentrations
was performed (Amis 2000 mass spectrometer, Innovision). The patient,
unaware of the timing of the test, breathed pure nitrogen for 2 to 8
breaths. This was repeated 10 to 15 times to provide a wide range of
O2 saturations from 75% to 100%, with 2-minute
intervals of air breathing between exposures to allow
O2 saturation and end-tidal
CO2 to return to the patient’s baseline.
Arterial O2 saturation was measured
with a pulse oximeter (model N-200E, Nellcor). The average of the 2
largest consecutive breaths that gave the highest ventilation after the
hypoxic stimulus was used to calculate maximal ventilation. The
peripheral chemosensitivity was expressed as the slope of
the regression line relating ventilation to arterial
O2 saturation (in L ·
min-1 ·
SaO2-1).11 12
Effect of Suppression of Peripheral Chemoreceptors on
Cyclical Breathing
Transient Hyperoxic Deactivation of Peripheral
Chemoreceptors
Eight patients with a reproducible cyclical respiratory pattern
underwent a 3-phase protocol (20-minute phases) during which they
breathed room air (phase I), 100% O2 delivered
via mask (60% O2 concentration in breathing air,
phase II), and finally room air (phase III). During the protocol,
respiration was recorded, and stable 15-minute periods at the end
of each phase were selected and subjected to spectral
analysis.
Effect of Dihydrocodeine on Cyclical Respiration
We have previously reported that dihydrocodeine decreases
peripheral chemosensitivity in CHF.13 Eight
patients with a cyclical respiratory pattern received placebo or
dihydrocodeine (1 mg/kg body wt) on 2 separate days in a randomized
double-blind design. One hour later, a 30-minute recording of
the respiratory signal followed by the assessment of
peripheral chemosensitivity was performed.
Statistical Analysis
Data are given as mean±SD. The natural log of the components of
heart rate variability (HRV) and peripheral
chemosensitivity were computed to correct for a skewed distribution.
The Student paired t test and ANOVA with the Fisher post hoc
test were performed as appropriate. Survival analysis was
performed by use of the Cox proportional hazards model. Kaplan-Meier
cumulative survival curves were constructed and compared using the
Mantel-Haenszel log-rank test. A value of P<0.05 was
considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
We prospectively identified 92 suitable patients for the study, and 74 were enrolled (Table 1
).
The reasons for exclusion were unwillingness to participate (n=14) or
technical problems in the analysis of respiratory data
(n=4).
|
Clinical Characteristics of Patients With Oscillatory
Breathing Patterns
Forty-nine (66%) CHF patients demonstrated a cyclical pattern of
respiration. The mean central frequency of this peak was 0.022±0.007
Hz (range, 0.007 to 0.041 Hz), which corresponded with a mean cycle
length of cyclical breathing of 50±21 seconds (25 to 143 seconds).
Among these patients, in 22 (30% overall) a CSR-like pattern (central
frequency 0.020±0.008 Hz) was observed (Figure 1
), whereas the
remaining 27 (36% overall) had a PB pattern (central frequency
0.024±0.006 Hz) (Figure 2).
The clinical data of patients with CSR, PB, or normal breathing (NB)
are presented in Table 2. There
was no difference in age, etiology, therapy, or cardiorespiratory
function between these groups, apart from more severe symptoms (NYHA
functional class) in patients with CSR and PB versus patients with NB
(P<0.05). Ambulatory 24-hour ECG monitoring was performed
in 62 (84%) patients: 19 CSR, 23 PB, and 20 NB. Nonsustained
ventricular tachycardia (3 consecutive
ventricular ectopic beats with a rate >100/min lasting
<30 seconds) was present in 10 (53%) CSR and 12 (52%) PB
patients compared with 2 (10%) NB patients (P<0.01).
|
Autonomic Balance in Patients With Cyclical Breathing
Patients from all 3 groups had similar resting heart rates. There
was no difference in HRV spectral components between patients with CSR
and with PB. Compared with the NB group, patients with cyclical
breathing revealed a different HRV profile, characterized by a
depressed LF component and a more predominant VLF rhythm (Table 2).
We assessed whether a cyclical respiratory pattern coincided with the
occurrence of the VLF rhythm in heart rate and blood pressure, defined
as a distinct peak within the VLF band of the R-R interval spectrum and
systolic blood pressure spectrum. Forty-eight patients (65%)
had a VLF rhythm in HRV (96% CSR versus 78% PB versus 24% NB,
P<0.001), and 44 patients (62%) had a VLF rhythm in the
systolic blood pressure spectrum (90% CSR versus 67% PB
versus 32% NB, P<0.05). Within the VLF band, 17 patients
revealed a significant coherence (>0.5) between the
oscillations in respiration and R-R interval (Figure 3), and 15 patients revealed a
significant coherence between respiration and systolic blood
pressure (Figure 3).
|
Baroreflex sensitivity was assessed in 35 (47%) patients randomly
chosen from the entire population: 12 CSR, 11 PB, and 12 NB. Patients
with CSR and PB exhibited severely depressed baroreceptor activity
compared with NB patients (Table 2).
Respiratory Disorders and Prognosis
At the end of follow-up in July 1998 (mean follow-up 838±315
days, >2 years in all who survived, 100% follow-up), there were 21
(28%) deaths (mean time to death 524±366 days, range 13 to 1321
days). Eighteen patients (37%) with a cyclical respiratory pattern (12
PB and 6 CSR) died; 3 NB patients (12%) died. Univariate
Cox proportional hazards analysis identified peak
O2 consumption <14 mL ·
kg-1 · min-1
(P=0.03), NYHA class III or IV (P=0.008), and a
cyclical respiration (relative risk 9.41, P=0.003), as
predictors of 2-year survival. Multivariate
analysis revealed that an abnormal breathing pattern was
related to death independent of peak O2
consumption (P=0.04) and NYHA class (P=0.06). The
2-year survival was 67% (95% CI, 54% to 80%) for patients who had
cyclical respiratory pattern versus 96% (88% to 100%) among NB
patients (P=0.008).
Peripheral Chemosensitivity and Cyclical
Breathing
Peripheral chemoreflex was evaluated in 53 (72%)
patients randomly selected from the study population: 15 CSR, 21 PB,
and 17 NB. None was hypoxemic at baseline: arterial
O2 saturation values ranged from 96% to 100%
(mean baseline saturation was 98.8%, 99.1%, and 99.3% for CSR, PB,
and NB, respectively). Peripheral chemosensitivity was
similar in patients with CSR and PB but significantly higher in those
patients compared with NB patients (P<0.005 in both
comparisons) (Table 2).
Effect of Transient Hyperoxic Deactivation of
Peripheral Chemoreceptors on Cyclic Respiratory
Pattern
In 8 patients with reproducible cyclical breathing who were
acutely exposed to hyperoxia, hyperoxic conditions abolished the
cyclical respiratory pattern in 7 patients, and when patients breathed
room air again, CSR or PB was restored in 4 patients within 20 minutes
(Figure 4).
|
Effect of Dihydrocodeine on the Cyclical Respiratory
Pattern
There was a significant fall in peripheral
chemosensitivity after dihydrocodeine administration compared with
placebo (0.66±0.49 versus 0.31±0.21 L ·
min-1 ·
%SaO2-1,
P<0.05). In 4 patients with PB after placebo, a normal
respiratory pattern was restored after dihydrocodeine administration.
In 2 patients who demonstrated CSR after placebo, dihydrocodeine
administration resulted in changes in the respiratory pattern toward
PB.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The main findings of the present study are that an oscillatory respiratory pattern is not a surrogate of the severity of CHF but, rather, a marker of abnormal autonomic balance and reflex function. Augmented peripheral chemosensitivity may be an important factor in the genesis of the oscillatory breathing patterns in CHF. The potential importance of cyclical respiratory pattern during wakefulness as a predictor of an increased prevalence of ventricular arrhythmias and a poor outcome has been also demonstrated.
In CHF, sleep-related breathing disorders worsen the patients’ symptoms, deteriorate cardiorespiratory function, and unfavorably influence outcome.2 14 A similar cyclical respiratory pattern commonly occurs during daytime resting conditions and during exercise in patients with stable CHF.5 6 We7 and the others6 have linked cyclical breathing with slow oscillations within the cardiovascular system, suggesting the existence a slow cardiorespiratory rhythm in patients with CHF. Although PB or CSR during the daytime may carry an important clinical meaning, there are few studies investigating this phenomenon.4 5 6
We found that a cyclical respiratory pattern during the daytime was common in patients with stable compensated CHF. We did not observe a significant difference in the clinical parameters of patients with oscillatory breathing compared with patients with NB, apart from a higher NYHA class in the former group. However, we did not measure hemodynamic parameters; therefore, we could not exclude the possibility of more compromised hemodynamic status in those with PB/CSR.
Patients with PB and CSR had a similar incidence (
50%) of
nonsustained ventricular tachycardia on Holter
recordings, which was significantly higher than that for
patients with NB. The association between CSR at night, episodes of
O2 desaturation, and arrhythmogenesis in CHF has
been documented.3 Because sleep studies were not routinely
performed, we do not know how many patients also exhibited classic CSR
with episodes of hypoxemia at night and whether this was a cause of the
higher incidence of nonsustained ventricular
tachycardia. However, in the present study, compared
with PB, a CSR-like pattern was not associated with any further
increase in the complexity and severity of ventricular
arrhythmias, suggesting that the occurrence of cyclical
breathing pattern (either genuine PB or CSR-like) may be a marker of an
increased risk of ventricular tachycardia.
Another new finding of the present study was that the presence of the oscillatory breathing during daytime identified patients with poor outcome, independent of the clinical parameters. There are a few reports investigating the impact of sleep-related breathing disorders on prognosis, but these studies involved smaller numbers of patients and conflicting results.4 14 Recently, Andreas et al4 found that CSR during the daytime but not during sleep had an important prognostic value.
We used the analysis of HRV and blood pressure variability as a tool to investigate sympathovagal balance. Compared with patients with NB, patients with CSR and PB demonstrated a similar pattern of HRV characterized by a significant decrease in the power within the LF band. Six patients had undetectable power within the LF band of the HRV spectrum; all of them exhibited periodic respiration (2 CSR and 4 PB). Reduction of, or absence of, the LF component of HRV could be potentially caused by a severely reduced peripheral target responsiveness with concomitant impairment in baroreflex circulatory regulation or by the recently suggested reduced central rhythmicity in autonomic outflow.15 Although we are not able to conclude which of these mechanisms would act in patients with PB, our findings confirm the association of cyclical respiration with severe autonomic imbalance. The clinical importance of this relationship can be only a matter of speculation. It has been documented that in normal subjects and in patients with obstructive sleep apnea, hypoxia, hypercapnia, and arousal are associated with increased sympathetic drive.16 17 In CHF, sympathetic overactivity contributes to ventricular arrhythmias18 and is also an independent prognostic factor.19 Thus, there may be a link between oscillatory breathing and the increased incidence of ventricular tachycardia and poorer outcome via severe autonomic imbalance.
Classic CSR is often viewed as the consequence of the instability in the feedback system controlling ventilation.20 The following factors could be responsible for the oscillatory respiration in CHF: an increase in controller gain (increased sensitivity to arterial O2 and CO2 changes), reduction in system damping (a decrease in total body stores of O2 and CO2), and a delay in information transfer (circulation time between lungs and brain).9 20 21 The increased chemoreceptor drive may represent the high controller gain, whereby small changes in O2 and CO2 can result in inappropriately large alterations of the system output.9 20 Therefore, overactive peripheral chemoreceptors may be responsible for the generation of oscillatory breathing.
We have previously shown an importance of peripheral chemoreceptors in the genesis of the slow rhythms in heart rate and blood pressure.7 In the present study, we demonstrated peripheral chemoreceptors to be overactive in patients with CSR/PB, and in the physiological experiments, we showed the importance of peripheral chemoreceptors in the genesis of the oscillatory breathing patterns. Breathing with O2 abolished the rhythmic oscillations in respiration, but these cyclical patterns emerged again when breathing normal room air. Supplemental O2 therapy has been shown to reduce CSR during sleep and also to improve exercise capacity in CHF patients.22 23 The mechanisms of the favorable influence of O2 have not been investigated in these studies, but an effect on peripheral chemoreceptors should not be neglected. Dihydrocodeine can reduce breathlessness and improve exercise tolerance in CHF, most likely by a reduction in chemosensitivity.13 In the present study, dihydrocodeine administration caused a decrease in peripheral chemosensitivity (-40% versus placebo) with concomitant changes in the periodic respiratory pattern.
Another interesting finding is the lack of any significant difference in clinical parameters, autonomic indices, and peripheral chemosensitivity between CHF patients with PB and those with true CSR. We hypothesize that both oscillatory breathing patterns (PB and CSR) occurring during wakefulness in CHF patients represent 2 aspects of the same phenomenon (which could be referred to as cyclical respiration), with similar pathophysiological mechanisms involved. In agreement with this hypothesis, we found that in some patients PB or CSR could alternatively be present on consecutive visits (data not shown).
The fact that baroreflex response was not measured in all patients could be a potential limitation of the present study. However, patients with baroreflex assessment were randomly chosen from the entire population and did not differ in the clinical characteristics from the remaining patients.
In summary, cyclical respiratory patterns during wakefulness are common in stable CHF and carry important clinical information. They occur on the background of impaired autonomic regulation and appear to be associated with an increased prevalence of cardiac arrhythmias and a poorer outcome. Enhanced activity of peripheral chemoreceptors may be an important factor in their genesis. Modulation of peripheral chemosensitivity could be a therapeutic option in CHF patients with cyclical breathing.
|
Acknowledgments |
|---|
Dr Ponikowski was supported by a research fellowship from the European Society of Cardiology; Dr Anker, by a postgraduate fellowship from Max-Delbrück-Centrum, Berlin, Germany; Dr Francis, by the British Heart Foundation; Dr Coats, by the Viscount Royston Trust; and Dr Piepoli, by the Wellcome Trust.
Received September 4, 1998; revision received July 16, 1999; accepted July 29, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Hanly PJ, Millar TW, Steljes DG, Baert R, Frais MA, Kryger MH. Respiration and abnormal sleep in patients with congestive heart failure. Chest. 1989;96:480–488.
2. Naughton MT, Benard DC, Liu PP, Rutherford R, Rankin F, Bradley TD. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995;152:473–479.[Abstract]
3.
Davies SW, John LM, Wedzicha JA, Lipkin DP. Overnight
studies in severe chronic heart failure: arrhythmias and oxygen
desaturation. Br Heart J. 1991;65:77–83.
4. Andreas S, Hagenah G, Moller C, Werner GS, Kreuzer H. Cheyne-Stokes respiration and prognosis in congestive heart failure. Am J Cardiol. 1996;78:1260–1264.[Medline] [Order article via Infotrieve]
5. Feld H, Priest S. A cyclic breathing pattern in patients with poor left ventricular function and compensated heart failure: a mild form of Cheyne-Stokes respiration? J Am Coll Cardiol. 1993;21:971–974.[Abstract]
6.
Mortara A, Sleight P, Pinna GD, Maestri R, Prpa A, La
Rovere MT, Cobelli F, Tavazzi L. Abnormal awake respiratory patterns
are common in chronic heart failure and may prevent evaluation of
autonomic tone by measures of heart rate variability.
Circulation. 1997;96:246–252.
7.
Ponikowski P, Chua TP, Piepoli M, Amadi AA, Harrington
D, Webb-Peploe K, Volterrani M, Colombo R, Mazzuero G, Giordano A,
Coats AJS. Chemoreceptor dependence of very low frequency rhythms in
advanced chronic heart failure. Am J Physiol. 1997;272:H438–H447.
8.
Ponikowski P, Chua TP, Piepoli M, Ondusova D,
Webb-Peploe K, Harrington D, Anker SD, Volterrani M, Colombo R,
Mazzuero G, Giordano A, Coats AJS. Augmented peripheral
chemosensitivity as a potential input to baroreflex impairment and
autonomic imbalance in chronic heart failure. Circulation. 1997;96:2586–2994.
9.
Lahiri S, Hsiao C, Zhang R, Mokashi A, Nishino T.
Peripheral chemoreceptors in respiratory
oscillations. J Appl Physiol. 1985;58:1901–1908.
10. Challis RE, Kitney RI. Biomedical signal processing: the power spectrum and coherence function. Med Biol Eng Comput. 1996;34:142–148.[Medline] [Order article via Infotrieve]
11. Chua TP, Clark AL, Amadi AA, Coats AJS. The relationship between chemosensitivity and the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol. 1996;27:650–657.[Abstract]
12. Edelman NH, Epstein PE, Lahiri S, Cherniack NS. Ventilatory responses to transient hypoxia and hypercapnia in man. Respir Physiol. 1973;17:302–314.[Medline] [Order article via Infotrieve]
13. Chua TP, Harrington D, Ponikowski P, Webb-Peploe K, Poole-Wilson PA, Coats AJS. Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol. 1997;29:147–52.[Abstract]
14. Hanly PJ, Zuberi-Khokhar NS. Increased mortality associated with Cheyne-Stokes respiration in patients with congestive heart failure. Am J Respir Crit Care Med. 1996;153:272–276.[Abstract]
15.
van de Borne P, Montano N, Pagani M, Oren R, Somers VK.
Absence of low-frequency variability of sympathetic nerve activity in
severe heart failure. Circulation. 1997;95:1449–1454.
16.
Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic
nerve activity during sleep in normal subjects. N Engl
J Med. 1993;328:303–307.
17. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897–1904.
18. Podrid PJ, Fogel RI, Fuchs TT. Ventricular arrhythmia in congestive heart failure. Am J Cardiol. 1992;69:82G–96G.[Medline] [Order article via Infotrieve]
19. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–823.[Abstract]
20.
Khoo MC, Kronauer RE, Strohl KP, Slutsky AS. Factors
inducing periodic breathing in humans: a general model. J
Appl Physiol. 1982;53:644–659.
21. Naughton M, Benard D, Tam A, Rutherford R, Bradley TD. Role of hyperventilation in the pathogenesis of cental sleep apneas in patients with congestive heart failure. Am Rev Respir Dis. 1993;148:330–338.[Medline] [Order article via Infotrieve]
22. Hanly PJ, Millar TW, Steljes DG, Baert R, Frais MA, Kryger MH. The effect of oxygen on respiration and sleep in patients with congestive heart failure. Ann Intern Med. 1989;111:777–782.
23. Andreas S, Clemens C, Sandholzer H, Figulla HR, Kreuzer H. Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure. J Am Coll Cardiol. 1996;27:1486–1490.[Abstract]
This article has been cited by other articles:
 |
|
 |
|
  R. Baruah, C. H. Manisty, A. Giannoni, K. Willson, Y. Mebrate, A. J. Baksi, B. Unsworth, N. Hadjiloizou, R. Sutton, J. Mayet, et al. Novel Use of Cardiac Pacemakers in Heart Failure to Dynamically Manipulate the Respiratory System Through Algorithmic Changes in Cardiac Output Circ Heart Fail, May 1, 2009; 2(3): 166 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Manisty, K. Willson, J. E. R. Davies, Z. I. Whinnett, R. Baruah, Y. Mebrate, P. Kanagaratnam, N. S. Peters, A. D. Hughes, J. Mayet, et al. Induction of oscillatory ventilation pattern using dynamic modulation of heart rate through a pacemaker Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R219 - R227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
T. Brack, I. Thuer, C. F. Clarenbach, O. Senn, G. Noll, E. W. Russi, and K. E. Bloch Daytime Cheyne-Stokes Respiration in Ambulatory Patients With Severe Congestive Heart Failure Is Associated With Increased Mortality Chest, November 1, 2007; 132(5): 1463 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. La Rovere, G. D. Pinna, R. Maestri, E. Robbi, A. Mortara, F. Fanfulla, O. Febo, and P. Sleight Clinical relevance of short-term day-time breathing disorders in chronic heart failure patients Eur J Heart Fail, September 1, 2007; 9(9): 949 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Johnson Management of end stage cardiac failure Postgrad. Med. J., June 1, 2007; 83(980): 395 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Xie, J. B. Skatrud, B. Morgan, B. Chenuel, R. Khayat, K. Reichmuth, J. Lin, and J. A. Dempsey Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans J. Physiol., November 15, 2006; 577(1): 319 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Manisty, K. Willson, R. Wensel, Z. I. Whinnett, J. E. Davies, W. L. G. Oldfield, J. Mayet, and D. P. Francis Development of respiratory control instability in heart failure: a novel approach to dissect the pathophysiological mechanisms J. Physiol., November 15, 2006; 577(1): 387 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 T. Brack, A. Jubran, F. Laghi, and M. J. Tobin Fluctuations in End-Expiratory Lung Volume during Cheyne-Stokes Respiration Am. J. Respir. Crit. Care Med., June 15, 2005; 171(12): 1408 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mortara, G. D. Pinna, P. Johnson, H. Dargie, M. T. La Rovere, P. Ponikowski, L. Tavazzi, P. Sleight, and on behalf of HHH Investigators A multi-country randomised trial of the role of a new telemonitoring system in CHF: the HHH study (Home or Hospital in Heart Failure). Rational, study design and protocol Eur. Heart J. Suppl., November 1, 2004; 6(suppl_F): F99 - F102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tulppo and H. V. Huikuri Origin and significance of heart rate variability J. Am. Coll. Cardiol., June 16, 2004; 43(12): 2278 - 2280. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. Koike, N. Shimizu, A. Tajima, T. Aizawa, L. T. Fu, H. Watanabe, and H. Itoh Relation Between Oscillatory Ventilation at Rest Before Cardiopulmonary Exercise Testing and Prognosis in Patients With Left Ventricular Dysfunction Chest, February 1, 2003; 123(2): 372 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
U. Corra, A. Giordano, E. Bosimini, A. Mezzani, M. Piepoli, A. J. S. Coats, and P. Giannuzzi Oscillatory Ventilation During Exercise in Patients With Chronic Heart Failure* : Clinical Correlates and Prognostic Implications Chest, May 1, 2002; 121(5): 1572 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. P. Ponikowski, T. P. Chua, D. P. Francis, A. Capucci, A. J.S. Coats, and M. F. Piepoli Muscle Ergoreceptor Overactivity Reflects Deterioration in Clinical Status and Cardiorespiratory Reflex Control in Chronic Heart Failure Circulation, November 6, 2001; 104(19): 2324 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ponikowski, T. P. Chua, S. D. Anker, D. P. Francis, W. Doehner, W. Banasiak, P. A. Poole-Wilson, M. F. Piepoli, and A. J.S. Coats Peripheral Chemoreceptor Hypersensitivity: An Ominous Sign in Patients With Chronic Heart Failure Circulation, July 31, 2001; 104(5): 544 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Clark, F. X. Kleber, G. Vietzke, K.-D. Wernecke, U. Bauer, C. Opitz, R. Wensel, A. Sperfeld, and S. Glaser Impairment of Ventilatory Efficiency in Heart Failure Response Circulation, May 8, 2001; 103 (18): e97 - e97. [Full Text] [PDF]
|
|
|
|
|
|
G. D. Pinna, R. Maestri, A. Mortara, M. T. L. Rovere, F. Fanfulla, and P. Sleight Periodic breathing in heart failure patients: testing the hypothesis of instability of the chemoreflex loop J Appl Physiol, December 1, 2000; 89(6): 2147 - 2157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Francis, K. Willson, L. C. Davies, A. J.S. Coats, and M. Piepoli Quantitative General Theory for Periodic Breathing in Chronic Heart Failure and its Clinical Implications Circulation, October 31, 2000; 102(18): 2214 - 2221. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||