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ABSTRACT |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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In patients with congestive heart failure (CHF), elevated, left ventricular (LV) volume might lead to
pulmonary congestion and hypocapnia, which would create a predisposition to the development of
Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). In addition, because LV volume affects cardiac output, it should influence the lengths of hyperpneas. We therefore evaluated LV volumes and transcutaneous PCO2 (PtcCO2) during wakefulness and stage 2 sleep in 16 patients with CHF
due to nonischemic dilated cardiomyopathy (NIDC). Data were then compared between those with (n = 7) and those without CSR-CSA (n = 9). LV end-diastolic volume (LVEDV) was significantly higher
in patients with than those without CSR-CSA (585 ± 118 versus 312 ± 41 ml, p < 0.05). Compared
with patients without CSR-CSA, those with CSR-CSA had lower mean stage 2 sleep PtcCO2 (36.3 ± 2.2 versus 41.2 ± 1.2 mm Hg, p < 0.05) and a lesser change in PtcCO2 from wakefulness to stage 2 sleep (
0.4 ± 0.3 versus 2.0 ± 0.4 mm Hg, p < 0.001). Among patients with CSR-CSA, hyperpnea
length was inversely related to LVEDV (R = 0.769, p = 0.043) owing to the direct relationship of cardiac output to LVEDV (R = 0.791, p = 0.034). We conclude that CSR-CSA in patients with CHF due to
NIDC is associated with increased LV volumes possibly through the direct or indirect influence of LV
volume on PaCO2 and cardiac output.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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It has been hypothesized that left ventricular (LV) dilation destabilizes respiratory pattern and predisposes patients with congestive heart failure (CHF) to the development of Cheyne-Stokes respiration (1). If true, then LV volume should be greater in CHF patients with Cheyne-Stokes respiration than in those without. Greater LV volume might also help to explain the higher mortality reported in CHF patients with, than those without, Cheyne-Stokes respiration with central sleep apnea (CSR-CSA), despite similar LV ejection fraction (2). Nevertheless, there are as yet no studies that have examined the potential role of increased LV volume in the pathophysiology of CSR-CSA in patients with CHF.
There are two key pathophysiologic features of CSR-CSA in patients with CHF; hyperventilation and hypocapnia, which trigger central apneas; and circulatory delay, which causes prolonged hyperpneas with the typical crescendo-decrescendo pattern of tidal volume (6). The normal rise in PaCO2 from wakefulness to sleep, due to withdrawal of the waking neural drive to breath, plays a critical role in preventing central apneas during sleep by keeping PaCO2 above the apneic threshold thus maintaining rhythmic breathing (8). If PaCO2 fails to increase at the onset of sleep, PaCO2 will remain low and close to the sleeping apneic threshold. Under these conditions, small reductions in PaCO2 trigger hypocapnic apneas (6, 7). The main determinant of periodic breathing cycle length, and of hyperpnea length, is circulatory delay which is inversely proportional to cardiac output (9). Therefore, periodic breathing cycles and hyperpneas are longer in patients with CHF and CSR-CSA than they are in patients with central sleep apnea who do not suffer from CHF (9).
How might increased LV volume relate to these two key pathophysiologic factors of CSR-CSA; hypocapnia and cardiac output? First, increases in LV volumes can lead to increases in LV filling pressures (10). Increased filling pressures not only predispose to pulmonary congestion, but are also associated with a tendency to hyperventilate due to stimulation of vagally innervated pulmonary irritant receptors (16, 17). The resulting hypocapnia should predispose to CSR-CSA (6). Second, according to Frank-Starling's law of the heart, the LV dilates to augment cardiac contractility in the failing heart in order to increase cardiac output (18). Therefore, if LV volume affects cardiac output it should also affect the lengths of hyperpneas and periodic breathing cycles of CSR-CSA. Accordingly, we hypothesized that in patients with CHF: LV volumes are larger in those with, than in those without CSR-CSA; larger LV volumes are associated with lower PaCO2 during sleep; and LV volume is related to hyperpnea length through its effect on cardiac output. To this end we studied the relationships among LV volume, PaCO2 and hyperpnea length of CSR-CSA in patients with CHF due to nonischemic dilated cardiomyopathy (NIDC).
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects
Consecutive patients with chronic CHF due to NIDC of unknown etiology were referred to the study from the congestive heart failure clinic of the Toronto Hospital. The diagnosis of NIDC was based on a reduced LV ejection fraction of < 45% and a dilated LV cavity as evidenced by an LV end-diastolic volume (LVEDV) index of > 80 ml/m2 determined by radionuclide angiography (see below) (19). In addition, the diagnosis of NIDC was confirmed by the absence of coronary artery disease on coronary angiography, or an absence of a history or electrocardiographic changes of ischemic heart disease on stress testing, or an absence of ischemic changes on myocardial perfusion imaging. Further inclusion criteria were: (1) at least a 6-m history of CHF documented by at least one clinical episode of pulmonary edema and chronic exertional dyspnea (New York Heart Association [NYHA] Classes II or III) despite appropriate pharmacologic therapy for CHF; (2) stable clinical status as evidenced by an absence of acute exacerbations of dyspnea or medication change for at least 1 month prior to entry; and (3) sinus rhythm. Exclusion criteria included: (1) a history or physical findings indicative of neurological lesions, (2) a history of pulmonary disease; and (3) use of sedative medications for sleep. The study protocol was approved by the Human Subjects Review Committee of the University of Toronto and all patients provided written informed consent prior to the study.
Left Ventricular Function and Volume
LV function was assessed using gated radionuclide angiography. Patients were studied while awake and in the supine position. Gated R-wave synchronous equilibrium angiography using the in vivo red blood cell labeling technique was performed with two separate intravenous injections: one with stannous pyrophosphate followed by a second with technetium99m pertechnetate. Cardiac imaging was performed with a gamma camera (Elscint APEX 409; Haifa, Israel) with a low energy all purpose collimator in the left anterior oblique view that provided optimal ventricular separation. Gated images were collected with a computer in a 64 by 64 matrix at a rate of at least 16 frames/cycle; the total acquisition time was 5 min per view. A simultaneous blood sample (10 ml) for absolute blood volume determination was also obtained in a preweighed syringe, and counted on top of a gamma camera afterwards with the exact time noted. Camera angulation and depth of the LV center of mass were determined using the method of Links and coworkers (20). LV time-activity curves were constructed through a variable LV region of interest generated by a semiautomated edge-detection program with minimal operator intervention for each frame of the composite cardiac cycle. LV ejection fraction was routinely determined as the difference between the end-systolic and the end-diastolic counts divided by end-diastolic counts.
To determine LVEDV, the ratio of the count rate from the LV and the concentration of radiotracer in the peripheral blood sample was calculated as:
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where u is the average linear attenuation coefficient and d is the depth
of the center of the LV in the body (20). The linear attenuation coefficient was assumed to be equal to that of water (u = 0.15 cm
1). The
count rate from the LV in the end-diastolic frame was calculated as:
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The calculation of LV end-systolic volume (LVESV) was analogous to that described for LVEDV. Determination of LV volumes by this method is highly reproducible and has been validated against angiographically determined LV volume (20). Stroke volume was calculated as the difference between LVEDV and LVESV. Cardiac output was calculated from the product of heart rate and stroke volume.
Sleep Studies
Following measurements of cardiac function, patients meeting all other inclusion criteria underwent overnight polysomnography to assess for the presence of CSR-CSA. Polysomnography was performed by personnel blind to the results of the cardiac function studies as described above. Standard techniques and scoring criteria were used for the determination of sleep stages (23). The electrocardiogram was recorded from a precordial lead. Thoracoabdominal movements were measured by a calibrated inductive plethysmograph (Respitrace; Ambulatory Monitoring, Inc., White Plains, NY) (6, 24). Transcutaneous PCO2 (PtcCO2) was recorded with a transcutaneous capnograph (Kontron Medical; Hoffman LaRoche, Basel, Switzerland) with the electrode placed on the anterior chest wall as previously described (6). Intrathoracic pressure was measured continuously by an esophageal balloon-catheter system (25) attached to a pressure transducer (Validyne, Northridge, CA). Oxyhemoglobin saturation (SaO2) was measured with an oximeter (Oxyshuttle; Sensormedics Corp., Anaheim, CA). The mean sleep SaO2 was calculated by averaging the high and low values for each 30-s epoch of sleep (6). Central apneas and hypopneas were identified by the absence of a tidal volume excursion for at least 10 s with no movements of the rib cage or abdomen, and were further confirmed by an absence of esophageal pressure swings. Central hypopneas were defined as a 50% or greater reduction in tidal volume from the baseline value, persisting for at least 10 s with proportional reductions in rib cage and abdominal movements, and in esophageal pressure swings (6, 26). Obstructive apneas and hypopneas were similarly defined except that paradoxical thoracoabdominal motion and increasing esophageal pressure swings had to be present despite an absence or a reduction in tidal volume, respectively. The apnea-hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep.
Patients were divided into those with CSR-CSA, who had an AHI
15 per h of sleep, and those without CSR-CSA (Non-CSR-CSA), who had an AHI < 15 per h of sleep. CSR-CSA was defined as a crescendo-decrescendo pattern of hyperpnea alternating with central apneas and hypopneas at a rate of 15 per h of sleep and in which apneas and hypopneas were predominantly (> 85%) central in nature
(6). Hyperpnea length was calculated as the time from the beginning
of inspiration during the ventilatory cycle and the onset of the subsequent apnea; apnea length was defined as the time between the onset
of expiration of the breath preceding a central apnea to the onset of
inspiration of the breath terminating the apnea. Cycle length was calculated as the sum of the hyperpnea and apnea lengths (Figure 1). The analysis of PtcCO2, hyperpnea length and periodic breathing cycle length was confined to stage 2 sleep because this was the predominant sleep stage (65.3 ± 4.7 and 70.5 ± 3.0% of total sleep time for the
Non-CSR-CSA and CSR-CSA group, respectively), and because the
majority of apneas in the CSR-CSA group were observed in stage 2 sleep (74.1 ± 2.9% of total apneas). Mean PtcCO2 was calculated by
averaging the highest and lowest PtcCO2 values for each 30-s epoch
throughout wakefulness and stage 2 sleep. Hyperpnea and periodic
breathing cycle lengths were determined from the average of 10 consecutive CSR-CSA cycles occurring at the onset of the first episode of
stage 2 sleep.
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Statistical Analysis
Two-tailed unpaired t tests were used to compare data for the Non-CSR-CSA and CSR-CSA groups. Cardiac functional class was compared by Wilcoxon rank sum test. Relationships among variables were examined by least-squares regression analyses. A p value < 0.05 was considered statistically significant. All results are expressed as mean ± SEM.
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RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Characteristics of the Patients
Sixteen patients (12 male and four female) with CHF due to NIDC were recruited; nine in the Non-CSR-CSA group and seven in the CSR-CSA group. The characteristics of the patients are shown in Table 1. Severe LV functional impairment, as indicated by a mean LV ejection fraction less than 25%, was observed in both groups. Although there was a tendency for LV ejection fraction to be lower in the CSR-CSA group than in the Non-CSR-CSA group, this difference was not statistically significant. Awake PaCO2 was significantly lower in the CSR-CSA than in the Non-CSR-CSA group. For the remaining characteristics, the two groups were comparable. In the Non-CSR-CSA group, seven patients were on diuretics, six on digoxin, eight on angiotensin converting enzyme inhibitors, and one on a beta-blocker. In the CSR-CSA group, seven patients were on diuretics, six on digoxin, seven on angiotensin converting enzyme inhibitors, and two on hydralazine.
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Polysomnographic Findings
As illustrated in Table 2, sleep structure and mean nocturnal SaO2 were similar in the two groups. However, mean stage 2 sleep PtcCO2 was lower in the CSR-CSA group than in the Non-CSR- CSA group (Figure 2). In the Non-CSR-CSA group there was a significant increase in PtcCO2 from wakefulness to stage 2 sleep (from 39.2 ± 1.2 to 41.2 ± 1.2 mm Hg, p < 0.001). However, no significant increase in PtcCO2 from wakefulness to stage 2 sleep was observed in the CSR-CSA group (from 36.7 ± 2.0 to 36.3 ± 2.2 mm Hg). The difference between the mean stage 2 sleep and mean wake PtcCO2 was significantly lower in the CSR-CSA than in the Non-CSR-CSA group (Figure 2). In the CSR-CSA group the mean apnea length was 23.9 ± 2.1 s, the mean hyperpnea length was 44.0 ± 6.8 s and the mean total periodic breathing cycle length was 68.1 ± 8.5 s.
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Stroke Volume, Cardiac Output, and Left Ventricular Volumes
No significant differences were found between the CSR-CSA and Non-CSR-CSA groups in either stroke volume (86.4 ± 20.7 versus 66.0 ± 9.6 ml, p = 0.35) or cardiac output (5.5 ± 1.3 versus 4.6 ± 0.7 l/min, p = 0.52). However, significantly higher LVEDV and LVESV, twice that of the Non-CSR-CSA group, were observed in the CSR-CSA group (Figure 3).
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There was no significant relationship between LVEDV and
either mean wake or mean stage 2 sleep PtcCO2. However, a
significant reciprocal relationship between the mean stage 2 sleep-mean wake PtcCO2 and LVEDV was observed (Figure
4). Within the CSR-CSA group there were significant inverse
relationships between total periodic breathing cycle length
and both cardiac output (R = 0.756, p < 0.05), and LVEDV
(R = 0.785, p < 0.05). However, since neither cardiac output
nor LVEDV correlated significantly with apnea length, these
relationships were due to significant inverse relationships between hyperpnea length and both cardiac output and LVEDV
(Figure 5). In addition, among patients with CSR-CSA, cardiac output was directly proportional to LVEDV (Figure 5).
Furthermore, there was a significant direct relationship between cardiac output and LVEDV within the entire group of
16 patients (R = 0.695, p = 0.003).
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DISCUSSION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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The present study provides novel insights into the pathophysiology of CSR-CSA in patients with CHF due to NIDC. First, the most striking finding of our study was that despite similar LV ejection fractions, LVEDV and LVESV were, on average, twice as high in patients with CSR-CSA than in those without CSR-CSA. These are the first data to provide direct evidence that the degree of LV dilation is greater among patients with, than those without CSR-CSA. Second, the increase in PtcCO2 from wakefulness to stage 2 sleep that was observed in the Non-CSR-CSA group was not seen in the CSR-CSA group. As a result, mean stage 2 sleep PtcCO2 was significantly lower in patients with CSR-CSA in agreement with our previous findings (6). However, the present findings extend those previous observations by showing that the degree of increase in PtcCO2 from wakefulness to stage 2 sleep is reciprocally related to LVEDV. Thus LV dilation is associated with an attenuation of the increase in PtcCO2 from wakefulness to sleep. This would tend to maintain PaCO2 close to the apneic threshold and predispose to central apneas secondary to fluctuations in PaCO2 below this threshold. Third, we found that the lengths of hyperpneas and of the periodic breathing cycles, in patients with CSR-CSA, were inversely related to LVEDV as well as to cardiac output.
The main clinical significance of CSR-CSA in patients with CHF is its association with higher mortality than in patients without CSR-CSA (2, 3). One factor that could explain higher mortality in patients with CSR-CSA is its association with elevated catecholamine activity, an important predictor of mortality (27, 28). However, higher mortality in patients with CSR-CSA does not appear to be due to lower LV ejection fraction, another important predictor of mortality in CHF (27). LV ejection fraction has consistently been shown to be similar in patients with and without CSR-CSA (2, 3, 6). The finding of similar LV ejection fraction in patients with and without CSR-CSA in the present study is in agreement with these previous reports.
Another factor that could contribute to higher mortality in CHF patients with CSR-CSA is increased heart size. It has long been suspected that patients with Cheyne-Stokes respiration have larger LV volumes than those without (1). However, the present study is the first to directly compare LV volumes in patients with and without CSR-CSA who have CHF due to NIDC. Despite similar LV ejection fractions, patients with CSR-CSA had LV volumes that were significantly higher than those without. Although LV ejection fractions were not significantly different in the CSR-CSA group than in the Non-CSR-CSA group, there was a tendency for lower LV ejection fractions in the CSR-CSA group. However, even when the LV ejection fractions were more evenly matched by excluding the patient with the lowest LV ejection fraction from the CSR-CSA group, and the two patients with the highest LV ejection fractions in the Non-CSR-CSA group (17.3 ± 5.0 versus 20.0 ± 2.3%, respectively, p = 0.62), LVEDV and LVESV were still significantly higher in the CSR-CSA group (616 ± 135 versus 298 ± 51 ml, p < 0.05, and 521 ± 126 versus 241 ± 46 ml, p < 0.05, respectively).
Studies have been carried out to assess the relative importance of decreases in LV ejection fraction versus increases in LV volumes as predictors of prognosis in patients with CHF. LV ejection fraction was found to be a major determinant of survival in those clinical studies that enrolled patients with CHF of diverse etiologies and with widely varying duration and severity of symptoms (4). However, recent investigations confined to patients with CHF of similar underlying etiology indicate that LV dimensions are primary predictors of survival both after myocardial infarction (29), and in patients with NIDC (5). Marked LV dilation indicates severe LV remodeling due to progression of underlying CHF (30) and is associated with the risk of ventricular arrhythmias (31). Patients with the greatest remodeling are those with the most aggressive underlying disease and the highest mortality.
We have previously shown that in patients with CHF, the most important pathophysiologic feature of CSR-CSA is a tendency to chronically hyperventilate maintaining PaCO2 close to the apneic threshold (6). In this setting, abrupt increases in ventilation, coupled with acute reductions in PaCO2 below the apneic threshold, trigger hypocapnic apneas during sleep. The mechanisms responsible for nocturnal hypocapnia in patients with CSR-CSA have not been fully elucidated. One possible explanation is hypoxia. However, as demonstrated previously (6), and in the present study, both awake PaO2 and mean nocturnal SaO2 in the CSR-CSA group are within normal limits and are practically identical to those in the Non-CSR-CSA group. Thus hypoxia is not likely to have played a primary role in causing hypocapnia in our patients. Another possible explanation is a primary increase in ventilatory responsiveness to chemical stimuli (32). However, we have previously shown that treatment of CSR-CSA by continuous positive airway pressure led to improvement in LV function in association with a reduction in ventilation and an increase in nocturnal PaCO2 (28). Since improvements in cardiac function led to reductions in ventilation and increases in PaCO2, those data suggested that hypocapnia was related to abnormalities of cardiac function.
The present findings also suggest that in patients with NIDC, the tendency to hyperventilate is at least partially related to abnormalities of cardiac function. We found that in conjunction with greater LV volumes, patients with CSR-CSA had a significantly lower PaCO2 while awake and lower mean PtcCO2 during stage 2 sleep. Moreover, an interesting finding of our study was that the greater the LVEDV, the less the rise in PaCO2 from wakefulness to stage 2 sleep. This relationship suggests that marked LV dilation in patients with NIDC is associated with a nonchemical drive to breathe that prevents the normal rise in PaCO2 during the transition from wakefulness to sleep.
According to the Frank-Starling law, the progressive dilation of the LV results in progressive increases in LV filling pressures, which contribute to the development of pulmonary congestion. A curvilinear relationship between increases in LV volumes and increases in LV pressures has been demonstrated (10). In patients with NIDC the diastolic pressure-volume relationship is displaced to the right due to reduced LV compliance (15). Experiments in animals and patients with CHF also demonstrate that increased LV filling pressures and pulmonary congestion are associated with reduced PaCO2 (16, 17). Therefore, our finding of a significantly greater LVEDV associated with a significantly lower mean stage 2 sleep PtcCO2 in the CSR-CSA group than in the Non-CSR-CSA group are consistent with those previous studies. The significant reciprocal relationship between LVEDV and the rise in PtcCO2 from wakefulness to sleep adds further support to the hypothesis that LV volume, through its possible effects on LV filling pressures and pulmonary congestion, influences ventilation and PaCO2. In addition, since LV filling pressures are not always elevated in patients with LV dilation, the question is raised as to whether there might be some more direct influence of LV dilation on ventilation and PaCO2, possibly via cardiac stretch or tension receptors. However, further research will be required to examine these possibilities.
The relationship between Cheyne-Stokes respiration cycle
length and circulatory delay has long been recognized (1, 35). However, the concept that two different mechanisms are involved in determining the lengths of apneas, and of hyperpneas, has only recently been described (9). On one hand, the
onset of central sleep apneas are caused by, and their lengths
are proportional to, reductions in PaCO2 below the apneic
threshold (6, 7, 36). On the other, hyperpnea and periodic
breathing cycle lengths are related directly to lung to carotid
body circulation time, and inversely to cardiac output (9). The
present finding of a significant inverse relationship between hyperpnea length and cardiac output confirmed our previous
findings in a different group of patients in whom cardiac output
was determined by a different technique
echocardiographic-Doppler (9). However, the present data add to those observations by showing that LVEDV is related to hyperpnea and periodic breathing cycle lengths through its effect on cardiac output. This observation is consistent with Frank-Starling's law of
the heart (18), which has recently been shown to be operative
even in end-stage, failing ventricles (37).
With respect to the technical aspects of measuring the volume of enlarged LVs, LV volumes by nuclear scanning have been validated against those determined by cardiac catheterization by Links and colleagues (20) up to 500 ml, and by Dehmer and associates (21) up to 800 ml. In the study of Dehmer and coworkers (21), the correlation coefficient was 0.95 and the 95% confidence limits were narrow and did not differ between lower and higher LV volumes. Also, self attenuation in very large LVs would tend to underestimate rather than overestimate, actual volume (22). Finally, since exactly the same technique was used to measure LV volumes in the CSR-CSA and Non-CSR-CSA patients, we are confident that LV volumes in the patients with CSR-CSA are larger than in those without it.
In summary, in patients with CHF secondary to NIDC, CSR-CSA appears to be a marker of poorer cardiac function than in those without CSR-CSA. This is manifest by a greater LV volume, despite similar LV ejection fraction and cardiac output. Increased LV volume, indicative of adverse cardiac remodeling, may be one factor contributing to the higher mortality observed in CHF patients with CSR-CSA compared to those without (2, 3). More pronounced LV dilation is associated with the absence of an increase in PtcCO2 during the transition from wakefulness to sleep as well as with lower mean stage 2 sleep PtcCO2, which is a key pathophysiologic factor in CSR-CSA (6). These factors should predispose to the development of hypocapnic central apneas during sleep (6). In addition, where CSR-CSA is present, the lengths of periodic breathing cycles and hyperpneas are inversely proportional to both LVEDV and to cardiac output.
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Footnotes |
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Correspondence and requests for reprints should be addressed to T. Douglas Bradley, M.D., 212-10 EN The Toronto Hospital (TGD), 200 Elizabeth Street, Toronto, ON, M5G 2C4 Canada.
(Received in original form December 23, 1996 and in revised form May 14, 1997).
Deceased. Was supported by a research fellowship from the Medical Research
Council of Canada. P. P. Liu is a Career Investigator of the Heart and Stroke Foundation. T. D. Bradley is a Career Scientist of the Ontario Ministry of Health.
Abbreviations: EEG, electroencephalogram; EMGsm, submental electromyogram; VT, tidal volume; Pes , esophageal pressure; SaO2, oxyhemoglobin saturation.
Acknowledgments: The authors acknowledge Ms. Yasmin Allidina for her technical assistance in performing and analyzing radionuclide angiograms.
Supported by operating grants MA-12422 and MT-11607 from the Medical Research Council of Canada. R. Tkacova is supported by a research fellowship from Respironics Inc.
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References |
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INTRODUCTION
METHODS
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DISCUSSION
REFERENCES
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1. Pryor, W. W.. 1951. Cheyne-Stokes respiration in patients with cardiac enlargement and prolonged circulation time. Circulation 4: 233-238 [Medline].
2. Findley, L. J., C. W. Zwillich, S. Ancoli-Israel, D. Kripke, G. Tisi, and K. M. Moser. 1985. Cheyne-Stokes breathing during sleep in patients with left ventricular heart failure. South. Med. J. 78: 11-15 [Medline].
3. Hanly, P. J., and N. S. Zuberi-Khokhar. 1996. Increased mortality associated with Cheyne-Stokes respiration in patients with congestive heart failure. Am. J. Respir. Crit. Care Med. 153: 272-276 [Abstract].
4. Likoff, M. J., S. Chandler, and H. R. Kay. 1987. Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am. J. Cardiol. 59: 634-638 [Medline].
5. Douglas, P. S., R. Morrow, A. Ioli, and N. Reichek. 1989. Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J. Am. Coll. Cardiol. 13: 311-315 [Abstract].
6. Naughton, M. T., D. Benard, A. Tam, R. Rutherford, and T. D. Bradley. 1993. Role of hyperventilation in the pathogenesis of central apneas in patients with congestive heart failure. Am. Rev. Respir. Dis. 148: 330-338 [Medline].
7. Xie, A., B. Wong, E. A. Phillipson, A. S. Slutsky, and T. D. Bradley. 1994. Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea. Am. J. Respir. Crit. Care Med. 150: 489-495 [Abstract].
8. Bradley, T. D., and E. A. Phillipson. 1992. Central sleep apnea. Clin. Chest Med. 13: 493-503 [Medline].
9. Hall, M. J., A. Xie, R. Rutherford, S. Ando, J. S. Floras, and T. D. Bradley. 1996. Cycle length of periodic breathing in patients with and without heart failure. Am. J. Respir. Crit. Care Med. 154: 376-381 [Abstract].
10.
Laks, M. M.,
D. Garner, and
H. J. C. Swan.
1967.
Volumes and compliances measured simultaneously in the right and left ventricles of the dog.
Circ. Res.
20:
565-569
11.
Noble, M. I. M.,
E. N. C. Milne,
R. J. Goerke,
E. Carlsson,
R. J. Domenech,
K. B. Saunders, and
J. I. E. Hoffman.
1969.
Left ventricular filling and diastolic pressure-volume relations in the conscious dog.
Circ.
Res.
24:
269-285
12.
Diamond, G.,
J. S. Forrester,
J. Hargis,
W. W. Parmley,
R. Danzig, and
H. J. C. Swan.
1971.
Diastolic pressure-volume relationship in the canine left ventricle.
Circ. Res.
29:
267-274
13.
Alderman, E. L., and
S. A. Glantz.
1976.
Acute hemodynamic interventions shift the diastolic pressure-volume curve in man.
Circulation
54:
662-672
14. Gaasch, W. H., M. A. Quinones, E. Waisser, H. G. Thiel, and J. K. Alexander. 1975. Diastolic compliance of the left ventricle in man. Am. J. Cardiol. 36: 193-201 [Medline].
15. Gaasch, W. H., and M. R. Zile. 1984. Evaluation of myocardial function in cardiomyopathic states. Prog. Cardiovasc. Dis. 27: 115-132 [Medline].
16. Bradley, T. D., R. M. Holloway, P. R. McLaughlin, B. L. Ross, J. Walters, and P. P. Liu. 1992. Cardiac output response to continuous positive airway pressure in congestive heart failure. Am. Rev. Respir. Dis. 145: 377-382 [Medline].
17. Churchill, E. D., and O. Cope. 1929. The rapid shallow breathing resulting from pulmonary congestion and edema. J. Exper. Med. 49: 531-537 [Abstract].
18. Spann, J. F., and J. W. Hurst. 1986. The recognition and management of heart failure. In J. W. Hurst, editor. The Heart. McGraw-Hill, New York. 345-369.
19. Manolio, T. A., K. L. Baughman, R. Rodeheffer, T. A. Pearson, J. D. Bristow, V. V. Michels, W. H. Abelmann, and W. R. Harlan. 1992. Prevalence and etiology of idiopathic dilated cardiomyopathy (Summary of a national heart, lung, and blood institute workshop). Am. J. Cardiol. 69: 1458-1466 [Medline].
20.
Links, J. M.,
L. C. Becker,
J. G. Schindledecker,
P. Guzman,
R. D. Burow,
E. L. Nickoloff,
P. O. Alderson, and
H. N. Wagner.
1982.
Measurement of absolute left ventricular volume from gated blood pool
studies.
Circulation
65:
82-91
21. Dehmer, G. J., S. E. Lewis, L. D. Hillis, D. Twieg, M. Falkoff, R. W. Parkey, and J. T. Willerson. 1980. Nongeometric determination of left ventricular volumes from equilibrium blood pool scans. Am. J. Cardiol. 45: 293-300 [Medline].
22.
Massie, B. M.,
B. L. Kramer,
E. W. Gertz, and
S. G. Henderson.
1982.
Radionuclide measurements of left ventricular volume: comparison of
geometric and counts-based methods.
Circulation
65:
725-730
23. Rechtschaffen, A., and A. A. Kales. 1968. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. National Institutes of Health, Washington, DC. Publication No. 204.
24. Chadha, T. S., H. Watson, S. Birch, G. A. Jenouri, A. W. Schneider, M. A. Cohn, and M. A. Sackner. 1982. Validation of respiratory inductive plethysmography using different calibration procedures. Am. Rev. Respir. Dis. 125: 644-649 [Medline].
25.
Milic-Emili, J.,
J. Mead,
J. M. Turner, and
E. M. Glauser.
1964.
Improved technique for estimating pleural pressure from esophageal balloons.
J. Appl. Physiol.
19:
207-211
26. Gould, G. A., K. J. Whyte, M. A. A. Airlie, J. R. Cateral, C. M. Shapiro, and N. J. Douglas. 1988. The sleep hypopnea syndrome. Am. Rev. Respir. Dis. 137: 895-898 [Medline].
27. Cohn, J. N., G. R. Johnson, R. Shabetai, H. Loeb, F. Tristani, T. Rector, R. Smith, and R. Fletcher. 1993. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. Circulation 87[Suppl. VI]:VI-5-VI-16.
28. Naughton, M. T., D. C. Benard, P. P. Liu, R. Rutherford, F. Rankin, and T. D. Bradley. 1995. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am. J. Respir. Crit. Care Med. 152: 473-479 [Abstract].
29.
White, H. D.,
R. M. Norris,
M. A. Brown,
P. W. T. Brandt,
R. M. L. Whitlock, and
C. J. Wild.
1987.
Left ventricular end-systolic volume as
the major determinant of survival after recovery from myocardial infarction.
Circulation
76:
44-51
30. Yi, G., P. J. Keeling, J. H. Goldman, H. Jian, J. Poloniecki, and W. J. McKenna. 1995. Prognostic significance of spectral turbulence analysis of the signal-averaged electrocardiogram in patients with idiopathic dilated cardiomyopathy. Am. J. Cardiol. 75: 494-497 [Medline].
31. Francis, G. S.. 1986. Development of arrhythmias in the patient with congestive heart failure: pathophysiology, prevalence, and prognosis. Am. J. Cardiol. 57: 3B-7B [Medline].
32. Wilcox, I., R. R. Grunstein, F. L. Collins, M. Berthon-Jones, D. T. Kelly, and C. E. Sullivan. 1993. The role of central chemosensitivity in central apnea and heart failure. Sleep 16: S37-S38 [Medline].
33.
Khoo, M. C. K.,
A. Gottschalk, and
A. I. Pack.
1991.
Sleep-induced periodic breathing and apnea: a theoretical study.
J. Appl. Physiol.
70:
2014-2024
34. Ahmed, M., C. Serrette, M. H. Kryger, and N. R. Anthonisen. 1994. Ventilatory instability in patients with congestive heart failure and nocturnal Cheyne-Stokes breathing. Sleep 17: 527-534 [Medline].
35.
Longobardo, G. S.,
N. S. Cherniack, and
A. P. Fishman.
1966.
Cheyne-Stokes breathing produced by a model of the human respiratory system.
J. Appl. Physiol.
21:
1839-1846
36.
Berssenbrugge, A.,
J. Dempsey,
C. Iber,
J. Skatrud, and
P. Wilson.
1983.
Mechanisms of hypoxia-induced periodic breathing during sleep in
humans.
J. Physiol.
343:
507-524
37.
Holubarsch, Ch.,
T. Ruf,
D. J. Goldstein,
R. C. Ashton,
W. Nickl,
B. Pieske,
K. Pioch,
J. Ludermann,
S. Wiesner,
G. Hasenfuss,
H. Posival,
H. Just, and
D. Burkhoff.
1996.
Existence of the Frank-Starling mechanism in the failing human heart: investigations on the organ, tissue,
and sarcomere levels.
Circulation
94:
683-689
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