Download Continuous positive airway pressure decreases myocardial oxygen

Clinical Science (2004) 106, 599–603 (Printed in Great Britain)
Continuous positive airway pressure decreases
myocardial oxygen consumption in heart failure
David M. KAYE∗ †, Darren MANSFIELD‡ and Matthew T. NAUGHTON‡
∗
Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, St Kilda Rd Central, Melbourne, VIC 8008,
Australia, †Department of Cardiovascular Medicine, Alfred Hospital, Commercial Rd, Prahran, VIC 3181, Australia, and
‡Department of Respiratory Medicine Alfred Hospital, Commercial Rd, Prahran, VIC 3181, Australia
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The aim of the present study was to investigate the effects of CPAP (continuous positive airway
pressure) support on myocardial energetics in patients with CHF (congestive heart failure). CPAP
has been shown to decrease left ventricular afterload and to produce favourable short- and longterm haemodynamic and neurohormonal benefits in CHF patients. The mechanisms responsible
for these actions are not completely understood. We measured the haemodynamic and myocardial
metabolic response to the acute (10 min) application of CPAP in CHF patients. Myocardial V̇ O2
(O2 consumption) and V̇ CO2 (CO2 production) were measured by simultaneous arterial and
coronary sinus blood sampling. The application of CPAP resulted in a significant decrease in left
ventricular stroke work (97 +
− 0.03 to
− 12 to 83 +
− 9 g · m; P < 0.05) and myocardial V̇ O2 (0.32 +
0.01
ml
of
O
0.25 +
/beat;
P
<
0.05).
Myocardial
mechanical
efficiency,
however,
was
unchanged.
2
−
CPAP application decreases myocardial work and V̇ O2 . This effect on myocardial energetics could
account for some of the favourable effects of CPAP in CHF patients.
INTRODUCTION
CHF (congestive heart failure) due to dilated cardiomyopathy is a complex disorder, marked by ventricular
dilation, increased LV (left ventricular) end-diastolic
and PCWP (pulmonary capillary wedge pressure) and
neurohormonal activation. In conjunction with these
observations, numerous studies have identified a range
of biochemical and molecular biological changes that
may account for the decrease in myocardial contractility
associated with CHF. Among these alterations in
myocardial metabolism, contractile protein expression
and calcium handling have been described in detail [1,2].
One of the key findings is that the contractile efficiency of
the heart is significantly decreased in CHF and, moreover,
that this may relate to a significant extent to the utilization
of O2 which is not translated into mechanical work [3].
In this context, it has been proposed that interventions that have been shown to exert positive influences
in CHF may, in part, be the result of favourable effects on myocardial energetics. For example, β-blockade
and ACE (angiotensin-converting enzyme) inhibition
have been shown to improve myocardial efficiency [4]
and to decrease myocardial V̇o2 (O2 consumption) [5]
respectively. In addition to these established pharmacological therapies for CHF, many other interventions
for CHF have emerged over the past decade. Among
these, the use of CPAP (continuous positive airway
pressure) support has emerged as a useful tool both in
the management of acute pulmonary congestion [6] and
for the management of sleep-disordered breathing [7,8].
Indeed, in relation to the acute clinical application of
CPAP in CHF patients, the application of positive intrathoracic pressure support has been shown to decrease LV
Key words: heart failure, myocardial metabolism, oxygen consumption, positive airway pressure.
Abbreviations: ACE, angiotensin-converting enzyme; CHF, congestive heart failure; CPAP, continuous positive airway pressure;
LV, left ventricular; LVW, LV work; MEE, myocardial energy expenditure; Meff, ventricular mechanical efficiency; PCWP, pulmonary
capillary wedge pressure; V̇co2 , CO2 production; V̇o2 , oxygen consumption.
Correspondence: Professor David M. Kaye (e-mail [email protected]).
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D. M. Kaye, D. Mansfield and M. T. Naughton
transmural pressure and to decrease ventricular volumes
[9,10]. Furthermore, more chronic application of CPAP
has been shown to exert favourable effects on LV function
and mitral regurgitant fraction [11]. In conjunction
with the direct mechanical actions, considerable evidence
also exists for a neuromodulatory effect of CPAP. We
have shown previously [12] that short term application
of CPAP decreases cardiac sympathetic tone, perhaps
by virtue of the accompanying decrease in transmural
pressure gradient.
Although clear benefits of CPAP therapy, both acutely
and in the chronic setting, are becoming apparent in
CHF patients, the precise mechanism(s) by which this
effect is mediated is unclear. Given the key role that
mechano–energetic uncoupling plays in CHF [13,14] and
the positive impact of CPAP on central haemodynamics
in CHF, we hypothesized in the present study that the
acute application of CPAP would impart a beneficial
influence on myocardial energetics in patients with CHF
during awake breathing.
METHODS
Patients
The present study consisted of 14 consecutive patients
undergoing right heart catheterization for evaluation of
heart failure status and/or heart transplant assessment at
the Alfred Hospital, Melbourne. This patient cohort has
been reported previously [12] in relation to the influence
of CPAP on sympathetic nervous activity. All patients
had an LV ejection fraction < 35 % and all had NYHA
(New York Heart Association) Class III symptoms of
CHF. All patients were treated with ACE inhibitors
and diuretics, and six were receiving β-adrenoceptor
antagonists at the time of study. The aetiology of CHF
was ischaemic cardiomyopathy in nine patients, nonischaemic dilated cardiomyopathy in four patients and
secondary to valvular heart disease in one patient. All
patients gave written informed consent, and the study
was performed with the approval of the Alfred Hospital
Ethics Review Committee.
Study protocol
All patients were instructed in the use of the CPAP device
(Sullivan Autoset T; ResMed, Sydney, Australia) on the
day before the catheterization study. Care was taken to
ensure that subjects were able to tolerate 10 cmH2 O of
applied pressure via a comfortably fitting nasal mask
without leaks, with a closed mouth for 10 min. On the
day of the experimental study, a radial arterial and right
internal jugular venous sheath were inserted under local
anaesthesia. A coronary sinus thermodilution catheter
(Webster Laboratories, Baldwin City, CA, U.S.A.) was
subsequently positioned in the coronary sinus for blood
sampling and blood flow measurement prior to and
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2004 The Biochemical Society
during the tenth minute of nasal CPAP. After completion
of these measurements, central haemodynamics were
again evaluated in the presence of continuing nasal CPAP.
Right heart pressures and cardiac output were determined
prior to and at the end of CPAP application.
Measurement of LV energetics
Myocardial V̇o2 and V̇co2 (CO2 production) were
calculated as the product of the coronary sinus blood flow
and the coronary sinus-arterial concentration difference
for each gas. The concentration of O2 and CO2 in blood
were calculated using standard methods [15,16]. LV work
(LVW) was determined using the formula:
LVW = cardiac output × (arterial systolic pressure
− wedge pressure) × 0.0136
Ventricular mechanical efficiency (Meff) was calculated
as the ratio of LVW to myocardial energy expenditure
(MEE). MEE was calculated according to the calorimetric
relationship [17]:
MEE ( J · min−1 ) = (0.08 × myocardial V̇o2 + 0.034
× myocardial V̇co2 ) × 4.18.
Calculation of Meff was also confirmed by the relationship:
Meff = LVW/(myocardial V̇o2 × 2.059).
Myocardial respiratory quotient (RQ) was calculated as:
RQ = myocardial V̇co2 /myocardial V̇o2 .
Statistical methods
Data are presented as means +
− S.E.M. Within group
comparisons were performed using a paired Student t test.
Correlations between continuous variables were analysed
using a Pearson correlation test, and where appropriate
multivariate analysis was employed. A P value < 0.05 was
considered statistically significant.
RESULTS
The application of CPAP did not significantly alter heart
rate (71 +
− 3 beats/min at baseline to 70 +
− 4 beats/min
after CPAP) or mean arterial blood pressure (79 +
−
3 mmHg at baseline to 81 +
− 4 mmHg after CPAP),
although there was a modest fall in cardiac output (4.8 +
−
0.3 litres/min at baseline to 4.4 +
− 0.2 litres/min after
CPAP; P < 0.05) and a rise in PCWP (17 +
− 3 mmHg at
baseline to 20 +
3
mmHg
after
CPAP;
P
<
0.05).
−
Effects of CPAP on O2 saturation and
myocardial metabolism
Administration of CPAP over 10 min resulted in a small,
but significant, increase in the arterial oxygen saturation
Continuous positive airway pressure decreases myocardial O2 consumption in heart failure
or cardiac output and changes in cardiac adrenergic
activity were evident (results not shown).
DISCUSSION
Figure 1 Relationship between the CPAP-mediated change
in LV stroke work and myocardial V̇ O2
level (97.4 +
− 0.4 % at baseline to 98.2 +
− 0.9 % after CPAP;
P < 0.05). Although there was no significant change in
arterial blood pressure, we did observe a statistically
−1
significant decrease in LV stroke work (97 +
− 12 g · m · m
−1
at baseline to 83 +
− 9 g · m · m after CPAP; P < 0.05).
This decrease in myocardial work was associated with
a significant diminution (P < 0.05) in myocardial V̇o2 ,
expressed either as ml of O2 /min (0.32 +
− 0.03 at baseline
to 0.25 +
0.01
after
CPAP)
or
in
terms
of V̇o2 /beat
−
+
(22.2 +
1.7
at
baseline
to
17.9
1.1
after
CPAP). In
−
−
association there was a trend for a decrease in myocardial
V̇co2 with the application of CPAP (21.2 +
− 1.7 ml/min
at baseline to 17.1 +
1.6
ml/min
after
CPAP;
P = 0.07).
−
No changes in myocardial contractile efficiency were
observed with the application of CPAP (15 +
− 2 % at
baseline compared with 16 +
1
%
after
CPAP).
The
−
myocardial respiratory quotient was not significantly
affected by CPAP use (0.98 +
− 0.04 at baseline compared
with 0.94 +
0.05
after
CPAP).
The observed changes in
−
myocardial V̇o2 that followed CPAP application showed
a modest relationship with the accompanying changes in
LV stroke work (Figure 1).
In a parallel study [12] performed on the current
patient cohort, we assessed the effects of acute CPAP on
cardiac sympathetic drive. This intervention was shown
to decrease cardiac noradrenaline spillover, as assessed by
isotope dilution methodology [12]. Accordingly, in the
present study, we also examined whether the observed
decrease in myocardial V̇o2 was related to the decrease in
cardiac adrenergic drive. In a univariate analysis, a weak
non-significant relationship between the CPAP-induced
change in myocardial V̇o2 and the change in cardiac
noradrenaline spillover was evident (r = 0.48, P = 0.10).
However, in a multivariate analysis performed to exclude
the confounding effects of changes in coronary sinus
blood flow, the relationship between myocardial V̇o2 and
cardiac noradrenaline spillover became weaker (P = 0.3).
Furthermore, no relationship between changes in PCWP
The key findings of the present study were that the
acute application of CPAP was associated with a fall
in LV stroke work and that this was accompanied by
a fall in myocardial V̇o2 . This observation is in keeping
with other studies that have demonstrated a favourable
haemodynamic effect of CPAP when applied acutely.
These actions include a decrease in LV afterload, LV
end-diastolic and end-systolic volumes and a decrease
in cardiac sympathetic activity [9,10,12,18]. The decrease in myocardial V̇o2 observed in our present study
is readily explained by the well characterized relationship
that exists between cardiac V̇o2 and the ventricular PVA
(pressure–volume area) [19]. Although in the present
study we did not measure the PVA or wall stress, LV
stroke work accounts for a significant proportion of the
PVA and, indeed, we confirmed a relationship between
the change in stroke work and the change in cardiac
O2 utilization. Nevertheless, the precise magnitude of
the haemodynamic influence of acute CPAP may have
been confounded by the fact that our study relied upon
the measurement of LV stroke work calculation by
thermodilution (consistent with usual clinical practice),
rather than by simultaneous micromanometer- and
conductance catheter-based measurement of LV volume
and pressure.
The strong relationship between PVA and myocardial
V̇o2 may also be influenced by catecholamines [19]. In the
present study, we could not establish that our previously
reported finding [12] of a decrease in adrenergic drive
to the heart was responsible for the change in cardiac
metabolic state. Furthermore, it is unlikely that a fall in
cardiac sympathetic drive would account for our findings,
given previous studies [3] which indicate that acute βblockade does not reduce myocardial V̇o2 in patients with
CHF when the heart rate is held constant.
In the present study, we did not detect a change
in myocardial contractile efficiency during CPAP. This
observation is also consistent with the studies of Suga
[19], which suggest that, at least over a modest range of
changes in loading condition, no change in contractile
efficiency is observed. During CPAP application we
documented a modest decrease in myocardial V̇co2 ,
without a change in the respiratory quotient. Little data
exists in man to indicate the time course or magnitude
of an expected change in myocardial V̇co2 for a given
change in workload.
The modest decrease in cardiac output that we observed in the present study is consistent with previous
observations made in patients with CHF, although the
response appears to be heterogeneous [20,21]. The precise
mechanism for a decrement in cardiac output may relate,
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D. M. Kaye, D. Mansfield and M. T. Naughton
in part, to a decrease in venous return and also to a
decrease in the work of breathing and consequently
blood flow to respiratory muscles. Our present study
also documented a rise in PCWP. This finding has also
been made previously in CHF and control subjects [10].
It should be noted that the measurement of the PCWP
in the context of CPAP is confounded by the direct
effect of CPAP on intrathoracic pressure, which was
not measured in the present study. In previous studies
[10], the application of CPAP at approx. 9 cmH2 O
pressure led to an increase in intrathoracic pressure of
approx. 4 cmH2 O, consistent with the observed rise in
wedge pressure in our present study. Furthermore, it is
relevant to note that CPAP has been used routinely in the
emergency room treatment of pulmonary oedema, and
this effect is probably mediated in part by its effect on
decreasing the hydraulic forces driving the accumulation
of interstitial fluid in this setting [6].
Although CPAP has become increasingly used as a
therapy for acute pulmonary oedema, the major interest
in the role of CPAP for the CHF patient has been in
the context of sleep-disordered breathing. It has been
estimated that up to 62% of CHF patients have evidence
of sleep apnoea [22], represented by obstructive sleep
apnoea and central sleep apnoea in approximately equal
proportions. The presence of sleep apnoea, in particular
central sleep apnoea, in CHF is associated with a poorer
prognosis [23,24], perhaps by virtue of its association with
a more decompensated haemodynamic profile [25]. With
this in mind, a number of investigators have examined the
longer term effects of nocturnal CPAP on LV function
and patient outcome during extended support periods. In
these studies, favourable effects on both haemodynamic
parameters [7,11] and possibly event-free survival have
been reported [8].
Although the precise mechanism for the chronic effects
of CPAP in patients with sleep-disordered breathing
remains unclear, it has been well documented that
nocturnal CPAP improves oxygenation and decreases
sympathetic activity [26]. In this respect it is possible that
some of the beneficial effects of longer term CPAP relate
to its capacity to decrease LV afterload and to decrease
ventricular volumes [9,10,27], in a manner analogous to
that afforded by ACE inhibition. Similarly, the inhibitory
influences of CPAP on sympathetic activity, whether by
decreasing hypoxic episodes and/or by decreasing LV
distension, could also be likened to the impact of βblockade in CHF to a degree. Of more direct relevance to
our present study, both ACE inhibition and β-blockade
also decrease myocardial V̇o2 [4,5], as we also observed
with CPAP. Although we did not include a healthy
control group in the present study, previous studies have
shown that, although CHF is associated with a decrease
in myocardial V̇o2 /beat in the face of lower work, the O2
cost of contractility is significantly higher in CHF [28,29].
Nevertheless, our present study is only of an acute nature,
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and it is not possible to directly implicate decreased O2
demand with the long-term improvements in myocardial
function that have been shown for CPAP in CHF.
Conclusions
The present study demonstrates that the acute application
of CPAP in CHF patients decreases myocardial V̇o2 ,
probably due to a decrease in myocardial work. Longterm studies are required to establish whether this
beneficial action contributes to the known favourable
effects of CPAP on ventricular performance and outcome
of patients in CHF.
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Received 8 August 2003/23 December 2003; accepted 3 February 2004
Published as Immediate Publication 3 February 2004, DOI 10.1042/CS20030265
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