Treatment of central sleep apnoea and Cheyne Stokes respiration in patients with heart failure:
nasal high-flow oxygen therapy?

Chronic heart failure (CHF) is a common health problem affecting 38 million
people worldwide. The treatment of heart failure is in general aimed at
reducing dyspnoea but is it is often overlooked that up to 62% of the patients
with heart failure have some moderate to severe sleep disordered breathing
(SDB). SDB leads to serious health complaints and worsens clinical outcomes
and may even be an antecedent risk factor for the development of overt heart
failure.
The 2 most common patterns of SDB are obstructive sleep apnoea (OSA) or central
sleep apnoea (CSA). In patients with heart failure, both may occur.
Furthermore, especially patients with severe CHF may exhibit a special form of
CSA with relative long cyclic episodes of crescendo/decrescendo respiration,
called Cheyne Stokes respiration (CSR).
Treatment of SDB in patient with heart failure is challenging. OSA is, in
general, adequately treated with a treatment that maintains upper airway
patency. The pathophysiological mechanisms and treatment of CSA/CSR, however,
are more complex. Hypocapnia, increased chemosensitivity, an higher apnoea
threshold, and a circulatory delay all contribute to ventilatory instability
and CSA/CSR in patients with heart failure.7
The goal of CSA treatment is to stabilise ventilation. Several treatment
options, ranging from pharmacological treatment with acetazolamide to nocturnal
oxygen therapy (NOT) and positive airway pressure therapies as continuous
positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) or
adaptive servo ventilation (ASV)) have been investigated, but interpretation of
the results of the studies is difficult to draw as these studies were small,
short-term and/or showed conflicting results in terms of improvement in
clinical outcomes. Secondly, to be even more cautions, some therapies might
even harm. In patients with a reduced left ventricular ejection fraction, ASV
therapy decreased the AHI index but increased mortality.16 It was suggested
that application of inspiratory and expiratory pressure levels, thereby
increasing intrathoracic pressure, might be harmful for an already diseased
heart.Furthermore, it was hypothesized that CSR is some sort of protective
mechanism in CHF patients.16 This suggests that a therapy probably should not
focus on total abandonment of CSR. Furthermore, the effects of CPAP and or
non-invasive ventilation or often hampered by a limited compliance with the
therapy. Overall, the optimal treatment of patients with CHF and CSA is
currently unknown.
Nasal high-flow therapy (nHFT) is the application of humidified heated
high-flow air, with or without the mixture with additional oxygen, through a
nasal catheter. This therapy combines the positive effects of a certain level
of continuous positive pharyngeal/airway pressure with application of
additional oxygen. We hypothesise that nHFT results into enough positive airway
pressure to maintain upper airway patency, to reduce pulmonary oedema because
of positive alveolar pressure, and to reduce left ventricular afterload. On the
other hand, the positive pressure achieved with nHFT is in comparison with CPAP
levels much lower and therefore a reduction in cardiac output because of high
intrathoracic pressure is not expected to occur. NOT has been hypothesized to
dampen the ventilatory overshooting characteristic of CSA due to a reduction in
peripheral chemosensitivity and may positively affect the heart as (deep)
repetitive oxygen desaturations are prevented. So, combining both modalities
with NFT might be beneficial. However, despite these theoretical potential
positive effects, however, nHFT may also promote hyperventilation due to the
high flow of air and thereby promote ventilatory instability.
A second advantage of nHFT that might be of importance is that compliance rates
of this therapy are shown to be very promising, as the nasal pillows of this
system are more comfortable compared to wearing a mask.CPAP results have been
shown to be limited because compliance rates were low. In this respect, the
mean disease alleviation, which is the product of therapeutic efficacy and
adjusted compliance expressed as percentage, might be better with nHFT and
might be of importance in affecting clinical outcomes.
To summarize, the effects of nHFT on CSA are unknown.
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The aim of the present pilot study is to investigate whether nHFT of different
settings (with different flow rates and additional amounts of oxygen)
stabilizes respiration and thus improves AHI index and promotes compliance
with the therapy in patients with known heart failure and CSA/CSR.

The study is a one-arm intervention pilot study, exploring the effects of 4-
weeks home nHFT in 10 patients with CHF and CSA.

High Flow Therapy which is the application of humidified heated high-flow air,
with or without the mixture with additional oxygen, through a nasal catheter.
This therapy combines the positive effects of a certain level of continuous
positive pharyngeal/airway pressure with application of additional oxygen.

Initiation of nHFT is considered as safe for several reasons. First, no serious
side effects of this therapy have been described in prior studies, although in
different, but also frail, patient groups. Secondly, patients are initiated on
the HFT during a titration night under direct supervision of the principle
researcher, which is a nurse specialist in the home mechanical ventilation
center in Groningen specialized on the treatment of patients with sleep apnea.
When there are problems with the nHFT, the patients can consult the principle
researcher and changes could immediately be made in the settings after
evaluation. For safety reasons, we will decide not to continue nHFt once during
the titration night AHI increases by more than 50%, regardless of the setting
applied.
Thirdly, patients with heart failure and CSA are not dependent of the therapy
for 24 hours. Although we advise to use the nHFT during the night, it is safe
to discontinue the therapy as long and often as they want to. Thereby, we
carefully take care that patients are able to remove the nasal catheter any
time when they are left alone with the high-flow device. Since it is easy to
remove the nasal catheter and patients with heart failure have adequate hand
functioning, we believe that patients are able to stop the therapy any moment
he/she wants. Therefore, we expect that the use of nHFT will be utmost safe.
Finally, the only invasive measurement that we will include are the measurement
of transdiaphragamtic pressure with the balloon catheters. These measurements
give some discomfort but are shown to be save in several patient groups. All
other measurements are noninvasive.