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Clinical Science (1995) 88, 173-178 (Printed in Great Britain)
I73
Haemodynamic effects of continuous positive airway
pressure in humans with normal and impaired left
ventricular function
Albert0 DE HOYOS, Peter P. LIU, Dean C. BENARD and T. Douglas BRADLEY
Centre for Cardiovascular Research and the Departments of Medicine, the Toronto Hospital and
Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
(Received 25 April/l9 August 1994 accepted 19 September 1994)
1. Continuous positive airway pressure increases
intrathoracic pressure, thereby decreasing left ventricular preload and afterload. We hypothesized that
there would be a dose-related alteration in cardiac
and stroke volume indices in response to continuous
positive airway pressure in normal subjects and
patients with congestive heart failure and that the
direction of response among those with heart failure
would be related to left ventricular preload.
2. Cardiac and stroke volume indices were measured
at baseline and after 10min of continuous positive
airway pressure at both 5 and 10cmH,O (0.5 and
0.99 kPa respectively) in 16 patients with heart failure
and five control subjects with normal cardiac function. Among the eight patients with heart failure and
elevated pulmonary capillary wedge pressure
( 212mmHg) ( 21.6 kPa), cardiac index increased
from 2.47 f0.34 at baseline to 2.91 f0.32 to 3.12 &
0.401min-'m-* (P<0.025) while on 5 and lOcm
H 2 0 of continuous positive airway pressure respectively. In the same patients stroke volume index
increased from 27.8 f 3.9 to 33.9 f 4.2 to 36.8 &
5.5 ml/m* (P<0.05). In contrast, in both the control
subjects and patients with heart failure and normal
pulmonary capillary wedge pressure ( < 12 mmHg)
there was a dose-related decrease in cardiac and
stroke volume indices while on continuous positive
airway pressure.
3. Continuous positive airway pressure causes doserelated increases in cardiac and stroke volume indices
among patients with chronic heart failure and
elevated left ventricular filling pressure. However, it
induces dose-related reductions in cardiac and stroke
volume indices among normal subjects as well as
patients with heart failure and normal left ventricular
filline Dressures.
INTRODUCTION
Until recently, positive-pressure breathing could
only be applied via an endotracheal tube. However, with the advent of non-invasive application
of continuous positive airway pressure (CPAP) via
a nasal or face mask, the use of CPAP has broadened to include out-patient treatment of sleep
apnoea [l] and emergency room treatment of
acute cardiogenic pulmonary oedema [2, 31. In the
latter case, CPAP improved Pao, and reduced the
need for intubation compared with medical therapy alone. More recently, nasal CPAP has been
shown to improve cardiac function in patients
with heart failure and co-existence obstructive
sleep apnoea or Cheyne-Strokes respiration [4, 51.
The beneficial effects of CPAP in heart failure
probably arise secondary to its haemodynamic
effects. However, these effects have not been well
defined.
Alterations in intrathoracic pressure resulting
from positive airway pressure affect cardiac output
by modifying cardiac preload and afterload [6-91.
We have demonstrated that a low level of CPAP,
5cmH,O (OSkPa), causes acute increases in cardiac output in patients with chronic heart failure
and elevated left ventricular filling pressures [lo].
However, potential dose-response relationships
were not examined. Clinically, it would be important to know if dose-response relationships existed,
as this would allow the titration of CPAP to the
appropriate level in a given patient in order to
provide the optimum haemodynamic response, just
as would be the case with a drug. Furthermore,
the effects of CPAP on haemodynamics in humans
without cardiac or pulmonary disease have not
been well studied. Therefore, to define better the
haemodynamic effects of CPAP, we studied the
dose-response effects of 5 and 10cmH,O (0.5 and
0.99kPa respectively) on stroke volume and cardiac output in subjects with normal and impaired
left ventricular function. The effects of 10 cmH,O
were assessed because this is a typical pressure
applied for the treatment of heart failure [2-51.
Key words: congestive heart failure, continuous positive airway pressure, haemodynamics.
Abbreviations: CHF, congestive heart failure; CI, cardiac index; CPAP, continuous positive airway pressure; PCWP, pulmonary capillary wedge pressure; SVI, stroke volume
index.
Correspondence: Dr T. Douglas Bradley, 212-10 Eaton North, The Toronto Hospital (TGD), 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
I74
A. de Hoyos et al.
METHODS
Subjects
Sixteen consecutive patients with chronic heart
failure undergoing cardiac catheterization as part
of the diagnostic investigation for dilated cardiomyopathy of unknown origin were entered into the
study. The entry criteria included: (1) at least a 6month history of heart failure as documented by
one or more episodes of worsening exertional
dyspnoea and radiographic evidence of cardiomegally and pulmonary congestion; (2) exertional dyspnoea (New York Heart Association class 2-4)
despite optimal medical therapy including digoxin,
diuretics and an angiotensin-converting enzyme
inhibitor; (3) a left ventricular ejection fraction of
<45% at rest as assessed in the supine position by
gated equilibrium radionuclide angiography within
1 week of the study; (4) stable clinical status as
evidenced by an absence of acute exacerbations of
dyspnoea or medication change for at least 30
days prior to the study; (5) sinus rhythm; and (6)
an absence of clinically detectable tricuspid regurgitation.
Based on the findings of previous studies in which
the main determinant of a positive cardiac output
response to positive airway pressure was an elevated
left ventricular filling pressure [ 10, 1 11, patients with
heart failure were divided into two groups according
to their baseline pulmonary capillary wedge pressure (wedge pressure); a heart failure-high wedge
pressure group in which wedge pressure was
2 12 mmHg (1.6 kPa) and a heart failure-low wedge
pressure group in which wedge pressure was
<12mmHg. A wedge pressure of 12mmHg was
chosen to divide the heart failure patients because
the highest wedge pressure in the normal control
group was 11 mmHg and 12 mmHg is considered to
be the upper limit of normal. Five additional
subjects with normal left ventricular ejection fraction ( > 60%) who were undergoing coronary angiography for investigation of chest pain of unknown
origin acted as controls. They were subsequently
found to have normal coronary arteries at angiography. All patients and normal control subjects
gave their written informed consent prior to entry
into the study. The protocol was approved by the
Ethics Committee for Human Experimentation of
the Toronto Hospital.
thermodilution method using lOml of saline at
room temperature via a Swan-Ganz catheter [121.
Cardiac output under each experimental condition
was taken as the average of three thermodilution
measurements which were within 10% of each other.
Cardiac index, stroke volume index and systemic
and pulmonary vascular resistances were then
derived. Baseline arterial blood gas tensions were
also analysed. All patients and control subjects had
a Pao, of >65mmHg (8.7kPa) and a Paco, of
< 45 mmHg (6.0 kPa) while breathing room air.
After baseline haemodynamic measurements were
obtained, CPAP was applied via a tight-fitting nasal
mask (Remstar Choice, Respirations, Murrysville,
PA, U.S.A.). During CPAP application, subjects
were instructed to keep their mouths tightly closed
and to breathe through their noses. CPAP at
5cmH,O was applied for lOmin, discontinued for
5min and reapplied for another 10min at
10cmH,O. Just prior to the end of each 10-min
application of positive airway pressure, haemodynamic measurements were repeated. In two
patients with heart failure and high wedge pressure,
haemodynamic measurements were repeated 10 min
after withdrawal from 10 cmH,O of airway pressure.
Once haemodynamic studies were completed, we
proceeded to coronary angiography and endomyocardial biopsies as appropriate.
Data analysis
Comparisons of baseline data among the three
groups were carried out by analysis of variance
(Systat, Intelligent Software, Evanston, IL, U.S.A.).
Haemodynamic variables were compared within
each of the three groups at baseline and while on
positive airway pressure of 5cmH,O
and
10cmH,O, by analysis of variance for repeated
measures. In order to examine relationships between
baseline wedge pressure and the cardiac index and
stroke volume index responses to CPAP, the change
in cardiac index and stroke volume index from
baseline to both 5 and 10cmH,O of CPAP were
regressed against baseline wedge pressure by the
Spearman rank order test. Data are expressed as
meanskSEM. A P-value of <0.05 was considered
to be statistically significant.
RESULTS
Characteristics of the patients
Protocol
All patients underwent right and left heart cath-
eterization. Baseline haemodynamic measurements
were made at the beginning of the experiment prior
to angiography and endomyocardial biopsy with the
patient breathing spontaneously through the nose.
Pressure measurements including right atrial pressure, pulmonary artery pressure, wedge pressure and
intrathoracic aortic pressure were obtained at endexpiration. Cardiac output was derived by the
Fifteen patients were shown to have normal
coronary angiograms and right ventricular endomyocardial biopsies consistent with idiopathic
dilated cardiomyopathy. The remaining patient was
found to have triple-vessel coronary artery disease.
Eight patients with heart failure had a baseline
wedge pressure 2 12 mmHg and eight had a wedge
pressure < 12mmHg. As shown in Table 1, left
ventricular ejection fraction was higher in the
control group than in either of the heart failure
Positive airway pressure and heart failure
Table 1. Characteristics of the patients and control subjects. Data
are expressed as means & SEM; *P <0.025; **P <0.001. Abbreviations:
CHF, congestive heart failure; PCWP, pulmonary capillary wedge pressure;
LVEF, left ventricular ejection fraction; CI, cardiac index; SVI, stroke
volume index: HR. heart rate.
Controls
CHF-low PCWP
CHF-high PCWP
(n = 5)
(n=8)
(n=8)
I75
50 45
~
40n
I
~
50. I f 5.0
64.4k 0.9**
2.98f0.32
41.2+ 1.4
72.8 k 6 . 3
Age (years)
LVEF (%)
CI (Imin-lm-')
SVI (ml m - I )
HR (beatslmin)
4.5
4.0
5 3.5
I
2'o
I .5
42.3 Ifr 5.1
32.4 f 4.3
3.14+0.17
44.0 4.6
n.2 7.8
+
46.2 f 5.4
28.7 6.2
2.47 f0.34
27.5 f 3.9*
89.9 f6.4
1
'
E35
*
-
t
K
30 25
~
1
Baseline
CPAP
CPAP
5cmH,O
IOcmH,O
Fig. 2. Stroke volume index (SVI) at baseline and S'and 10cmHIO
of CPAP in the three groups. In the control group (a),
there was a
decremental reduction in SVI decreasing with increasing CPAP (from
41.2f 1.4 to 36.6k 1.9 t o 34.0k 1.7ml/m2). The same was true of the
CHF-low PCWP group (A)(from 44.0k4.6 to 43.0k4.1 t o
38.3k4.1 ml/m*). However, the opposite response was observed in the
CHF-high PCWP group (V),in which SVI increased incrementally with
increasing CPAP (from 27.8 k 3.9 t o 33.9 k 4 . 2 to 36.8 k 5.5 ml/ml). Note
that while on IOcmH,O of CPAP, SVls are similar in all three groups.
*P<0.05, tP<O.OI and $P<O.OOI for both 5 and IOcmH,O compared
with baseline. Abbreviations: as for Fig. I.
1
t
$
E
:
Baseline
CPAP
5cmH,O
CPAP
IOcmH,O
Fig. 1. Cardiac index (CI) response to CPAP of 5 and 10cmHIO in
the control (a),congestive heart failure (CHF)-low pulmonary
and CHFhigh PCWP groups
capillary wedge pressure (PCWP) (A)
(0).
Note the decremental reductions in CI among the control subjects
with increasing CPAP (from 2.98k0.33 t o 2.40+0.12 to 2.30+
0.18lmin-'mP). Similar results were observed in the CHF-low PCWP
group (from 3.20&0.15 to 2.92_+0.19 to 2.80_+0.271min-'m-'). In
contrast, the CHF-high PCWP group experienced an incremental augmentation in CI with increasing CPAP (from 2.47k0.34 to 2.91 f0.32 to
Also note that, while on CPAP of IOcmH,O. CI
3.IZf0.401min-'m-').
in the CHF-high PCWP group was higher than that on the same pressure in
the control and CHF-low PCWP groups and was similar t o the baseline CI
in these same two groups. **P<O.O25 at both 5 and IOcmH,O compared
with baseline.
groups (P<O.OOl) but there was no difference in left
ventricular ejection fraction between the heart
failure-high wedge pressure and low wedge pressure
groups. Stroke volume index was significantly lower
in the heart failure-high wedge pressure group
(P<O.O25) than in the other two groups.
Effect of CPAP on cardiac and stroke volume indices
As illustrated in Figs. 1 and 2 and Tables 1 and 2,
baseline haemodynamic indices among the heart
failure-low wedge pressure group resembled those
of the normal control group, indicating that heart
failure was haemodynamically well compensated. In
contrast, baseline haemodynamic indices among the
heart failure-high wedge pressure group were generally worse than in either the control or heart
failure-low wedge pressure groups.
Table 2. Right atrial and pulmonary capillary wedge pressures. *To
convert mmHg into kPa multiply by 0.1333. tP<O.OI, ttP<0.001 compared with baseline. $P<O.OOI compared with low PCWP and control
groups. Abbreviations: CPAP, continuous positive airway pressure; RAP,
right atrial pressure; otherwise as for Table I.
Baseline
CPAP 5
(% change)
CPAP 10
(% change)
Controls
RAP (mmHg)*
PCWP (mmHg)
4.2 k 0.9
8.0+ 1.1
6.4 f I .O (52)
7.8f 1.4(-2.5)
7.4 k0.8(76)t
9.8+ I.0(22.5)
CHF-low PCWP
RAP (mmHg)
PCWP (mmHg)
5.1 f0.7
7.3k0.8
7.5+0.8(47.0)
9.5_+0.9(30.1)
8.7 +0.6(70.5)tt
10.3f0.9(41.O)tt
CHF-high PCWP
RAP (mmHg)
PCWP (mmHg)
9.4+ 0.9$
21.2 k 3.5$
9.6 f0.7(2.l)
l 9 . 2 k 2.3 (-9.4)
20.2f 2.7 (-4.7)
I I.5
+ I.O(22.3)
Among control subjects there were dose-related
reductions in cardiac and stroke volume indices that
reached 22.8% and 17.5% below baseline, respectively, while on 10cmH,O of airway pressure. Heart
rate did not change significantly (from 72.8k6.3 to
66.4 & 3.5 to 68.4 & 6.3 beats/min). Similarly, among
the heart failure-low wedge pressure group, there
were dose-related reductions in cardiac and stroke
volume indices that averaged 12.5% and 13.0%
below baseline, respectively, at 10cmH,O. Again
there was no significant change in heart rate (from
77.4 & 7.8 to 72.0 & 7.7 to 76.3 & 7.9 beats/min). In
contrast, in the heart failure-high wedge pressure
group there were dose-related increases in cardiac
I76
A. de Hoyos et al.
and stroke volume indices averaging 26.3% and
32.4% above baseline, respectively, at 10cmH,O. In
the two patients in the heart failure-high wedge
pressure group in whom cardiac index was
remeasured after CPAP was removed, cardiac index
decreased back to the baseline level after withdrawal
of CPAP (from 1.71 Imin-' rn-, at baseline to
2.8 1 1 min m
on 10 cmH,O of airway pressure
to 1.811min-'m-2 10min after withdrawal of airway pressure in the first patient and from
2.051min-'m-2 at baseline to 3.211min-'m-2 on
10cmH,O to 2.121min-' m - 2 after withdrawal of
airway pressure in the second patient). There were
no significant changes in heart rate while on CPAP
in the heart failure-high wedge pressure group
(from 89.9 k 6.9 to 88.5 k 6.9 to 87.1 f 6.5 beats/min).
There were significant correlations between baseline wedge pressure and the change in cardiac and
stroke volume indices from baseline to airway pressure of 5cmH20 (r=0.690, P<O.OOl, and r=0.607,
P < 0.004, respectively) and from baseline to
10cmH20 (r=0.637, P<0.002, and r=0.635,
P < 0.002, respectively) for the data from all subjects.
Furthermore, if the patients with heart failure are
divided into thirds on the basis of their wedge
pressures, those six patients in the middle third (812 mmHg) had no significant change in cardiac
index on CPAP (from 3.14f0.40 at baseline to
3.30k0.33 on 5cmH,O of CPAP and to 3.25+
0.41 Imin-' m - 2 on 10cmH20 of CPAP). In contrast, the five patients with a wedge pressure of
< 8 mmHg all had reductions in cardiac indices on
both levels of CPAP, while the five patients with
wedge pressures of > 12 mmHg all experienced
increases in cardiac indices on both levels of CPAP.
Thus there appears to be an intermediate wedge
pressure or preload in which CPAP has a neutral
effect of cardiac output.
Effects of CPAP on wedge pressure, right atrial pressure
and vascular resistances
Baseline wedge pressures ranged from 5 to
11 mmHg (0.67-1.47 kPa) in both the control and
heart failure-low wedge pressure groups and from
12 to 33 mmHg (1.6-4.4 kPa) in the heart failurehigh wedge pressure group. Baseline right atrial
pressure and wedge pressure were significantly
higher in the heart failure-high wedge pressure
group than in the control and heart failure-low
wedge pressure groups ( P < 0.001) (Table 2). Among
the control and heart failure-low wedge pressure
groups there were dose-related increases in right
atrial pressure with increasing airway pressure.
However, in the heart failure-high wedge pressure
group there was no significant change in right atrial
pressure. Wedge pressure increased significantly in
the heart failure-low wedge pressure group
(P<O.OOl) but not in the control and heart failurehigh wedge pressure groups. Systemic vascular resis-
Table 3. lntravascular resistance. *P <0.05 compared with baseline.
Abbreviations: PVR, pulmonary vascular resistance; SVR, systemic vascular
resistance; otherwise as for Tables I and 2.
CPAP 5
(% change)
CPAP 10
(% change)
Controls
120+21
PVR (dynr-lcm-s)
SVR ( d y n s - l ~ m - ~ ) 1567+219
126+ 12(5)
1706+175(8.9)
I32 & 24 (10)
1753+280(11.9)
CHF-low PCWP
PVR (dynsC'cm-')
SVR (dyns-lcm-l)
101 + I 6
1278+97
102+ l3(0.9)
1372+ 137(7.4)
109+ 14(7.9)
14%+ 162(16.6)
CHF-high PCWP
PVR (dyn s- ' cm -')
SVR (dyns-lcm-')
214 70
1692+224
I99 59 ( - 7)
1351 +104-20.1)
I78 & 34 ( - 16.8)
1299&82(-23.2)*
Baseline
+
tance did not change significantly in the control and
heart failure-low wedge pressure groups while on
CPAP (Table 3). In contrast, within the heart
failure-high wedge pressure group, there was a
dose-related fall in systemic vascular resistance
( P < 0.05). This decrease in systemic vascular resistance was not accompanied by any significant
change in mean aortic pressure (from 94+8mmHg
to 95 8 mmHg to 96 f 8 mmHg). Pulmonary vascular resistance did not change significantly in any of
the three groups. No adverse effects were experienced by any of the subjects in this study.
DISCUSSION
We have demonstrated that in those patients
studied with heart failure and high wedge pressure,
cardiac and stroke volume indices increased
incrementally with increasing CPAP from 0 to 5 to
10 cmH,O. Conversely, in the heart failure group
with low wedge pressure, these indices fell
decrementally. In addition, among subjects with
normal cardiac function, cardiac and stroke volume
indices fell decrementally with increasing airway
pressures. Furthermore, there was a significant correlation between the baseline wedge pressure and
the magnitude of change in cardiac and stroke
volume indices while on CPAP of both 5 and
10 cmH20. Our results indicate that dose-related
haemodynamic effects occur in response to CPAP
and that these effects are most likely to be positive
in patients with heart failure and poorer haemodynamic status.
The effects of CPAP have not been well studied
in patients without cardiac or respiratory disease.
Our data show that CPAP produces a negative
cardiac output response in such subjects, as it does
with application of intermittent positive endexpiratory pressure [9]. When myocardial contractility and preload are normal, increases in
intrathoracic pressure reduce cardiac index in the
normal heart mainly through reductions in venous
return (i.e. preload) [S-10, 13-18]. Similar results
were observed in heart failure-low wedge pressure
Positive airway pressure and heart failure
patients who were haemodynamically well compensated.
In contrast, when left ventricular filling pressures
are elevated, reductions in preload secondary to
increased intrathoracic pressure may have beneficial
effects on cardiac output and stroke volume. Our
patients with heart failure and high wedge pressure
experienced significant increases in both cardiac and
stroke volume indices with application of CPAP.
These patients had relatively poorer haemodynamic
status than the heart failure-low wedge pressure
group. Although the mechanism for CPAP-induced
improvements in cardiac and stroke volume indices
could not be determined from the measurements
made herein, the most likely explanation is a reduction in left ventricular afterload.
We have recently shown in a preliminary report
[191 that CPAP reduces left ventricular transmural
pressure during systole in a dose-related manner by
increasing intrathoracic pressure, thereby decreasing
the gradient between intra-left ventricular and
intrathoracic pressure in patients with heart failure
[S, 14, 20, 213. Furthermore, there was a significant
reduction in systemic vascular resistance while on
positive airway pressure in the present study. Such
afterload-reducing effects generally lead to augmentations of cardiac output in the failing heart [13, 14,
15, 221. The absence of increases in heart rate while
on positive airway pressure suggests that increased
cardiac index was not due to increased sympathetic
nervous activity.
Improvements in cardiac and stroke volume
indices among the heart failure-high wedge pressure
group averaged 26.3 and 32.4% above baseline,
respectively, while on positive airway pressure of
10cmH,O. These improvements were similar to
those achieved acutely with inotropic and vasodilator drugs [l5, 22, 23, 241 and therefore could have
clinical significance for the treatment of heart failure
[4, 5, lo]. However, because positive airway pressure was applied for only 10min at each level, the
duration of the positive haemodynamic effects in the
heart failure-high wedge pressure group could not
be assessed. In the two patients in whom haemodynamics were reassessed 10 min after withdrawal of
positive airway pressure, cardiac and stroke volume
indices fell back to the baseline level. Thus our
findings could not explain the sustained
improvements in left ventricular systolic function
measured in the daytime observed in association
with application of CPAP overnight in patients with
chronic heart failure and sleep apnoea [4, 51.
Sustained application of CPAP will probably be
required to explore this long-term effect.
Baratz et al. [25] recently showed that CPAP
could augment cardiac index in some patients with
acute severe cardiogenic pulmonary oedema. However, they did not find any factors measured at
baseline, including wedge pressure, that were associated with a positive cardiac index response. Differences between their findings and ours were probably
177
related to differences in clinical status of patients
and their medical therapy. In Baratz et al.’s study
patients suffered mainly from ischaemic heart disease and were in acute pulmonary oedema with
hypoxia. Most were on supplemental oxygen, intravenous inotropes and vasodilators. In contrast, our
patients had chronic stable heart failure secondary,
in all but one, to idiopathic dilated cardiomyopathy.
Furthermore, our patients were not hypoxaemic and
were not on oxygen, intravenous inotropes or vasodilators. More importantly, Baratz et al. were able
to demonstrate an increase in cardiac index in half
their patients. Therefore, their study and ours are in
agreement in demonstrating that CPAP can augment cardiac and stroke volume indices in a substantial number of patients with acute or chronic
heart failure. However, ours is the first study to
demonstrate dose-response effects of CPAP on
haemodynamics in a group of stable patients with
predominantly idiopathic dilated cardiomyopathy
who were in sinus rhythm. Although our findings
are of physiological significance, further studies will
be required to determine the clinical safety and
efficacy of CPAP when applied for longer periods in
patients whose heart failure is poorly controlled.
ACKNOWLEDGMENTS
We are grateful for the assistance of Dr John D.
Parker in performing some of the haemodynamic
studies. This study was supported by operating
grants from the Medical Research Council of
Canada (MT 11607) and the Heart and Stroke
Foundation of Ontario. Albert0 de Hoyos is a
Fellow of the Medical Research Council of Canada,
and T. Douglas Bradley is a Career Scientist of the
Ontario Ministry of Health.
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