Review: Sleep-Disordered Breathing in Heart Failure

Simon G Pearse and Martin R Cowie

Imperial College London and Royal Brompton Hospital, London, UK.

Key-words: heart failure; sleep disordered breathing; diagnosis; treatment

Address for correspondence:

Professor Martin R Cowie MD MSc FRCP FRCP (Ed) FESCProfessor of CardiologyImperial College London (Royal Brompton Hospital)Dovehouse StreetLondon SW3 6LY

T: +442073518856F: +442073518148E: m.cowie@imperial.ac.uk

Acknowledgement: MRC’s salary is supported by the NIHR Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital, London.

Declaration of interests: MRC is the co-Principal Investigator of the SERVE-HF Study, funded by ResMed, and has received research grants and honoraria for speaking on sleep disordered breathing from ResMed, and consultancy fees from Respicardia and Sorin. SGP’s salary is funded by Boston Scientific.

Word counts:Text: 4251 wordsAbstract: 241 words

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Abstract

Sleep-disordered breathing - comprising obstructive sleep apnoea (OSA), central sleep apnoea

(CSA), or a combination of the two - is found in over half of heart failure (HF) patients and

may have harmful effects on cardiac function, with swings in intra-thoracic pressure (and

therefore preload and afterload), blood pressure, and sympathetic activity, and repetitive

hypoxaemia. It is associated with reduced health-related quality of life, higher health care

utilisation, and a poor prognosis. Whilst continuous positive airways pressure (CPAP) is the

treatment of choice for patients with daytime sleepiness due to OSA, the optimal management

of CSA remains uncertain. There is much circumstantial evidence that the treatment of OSA

in HF patients with CPAP can improve symptoms, cardiac function, biomarkers of

cardiovascular disease, and quality of life, but the quality of evidence for an improvement in

mortality is weak. For systolic HF patients with CSA, the CANPAP trial did not demonstrate

an overall survival or hospitalisation advantage for CPAP. A minute-ventilation targeted PAP

therapy, adaptive servo-ventilation (ASV), can control CSA and improves several surrogate

markers of cardiovascular outcome, but in the recently-published SERVE-HF randomised

trial, ASV was associated with significantly increased mortality and no improvement in HF

hospitalisation or quality of life. Further research is needed to clarify the therapeutic rationale

for the treatment of CSA in HF. Cardiologists should have a high index of suspicion for SDB

in those with HF and work closely with sleep physicians to optimise patient management.

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Introduction

Heart failure (HF) affects around 2% of the adult population in developed countries; a figure

that rises to 10% in those over 70 years (1). Despite advances in therapy, HF continues to

confer a poor prognosis and more than half of patients hospitalised for HF die within 5 years

(2).

Sleep-disordered breathing (SDB) is increasingly recognised as a marker of poor prognosis in

patients with HF and a disease process that may accelerate the downward spiral of cardiac

dysfunction. Over 50% of patients with HF (with either preserved or reduced ejection

fraction) have SDB, which is around ten times the rate in the general population (3–5). In

current clinical practice, many patients remain undiagnosed. Older age, male gender,

increased body mass index, lower ejection fraction and the presence of atrial fibrillation are

independent predictors for the presence of SDB (6).

Despite increasing evidence of the impact of SDB, the European Society of Cardiology

guidelines on heart failure mention it only as a potential co-morbidity and suggest that

treatment “might be considered” (7). This review describes the aetiology and

pathophysiological effects of SDB, the current approach to diagnosis, and the treatment

options available.

Aetiology and classification of sleep-disordered breathing

SDB includes obstructive sleep apnoea (OSA), central sleep apnoea (CSA), or a combination

of both. In OSA, there is collapse of the pharynx during sleep with consequent upper airway

obstruction, often with snoring. Predisposing factors include obesity, a short neck and

retrognathism. In HF, rostral shift of fluid during sleep leads to pharyngeal oedema, which

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may exacerbate the tendency to obstruction (8). In CSA, the underlying abnormality is in the

regulation of breathing in the respiratory centres of the brainstem. In normal physiology,

minute ventilation during sleep is primarily regulated by chemoreceptors in the brainstem and

carotid bodies which trigger an increase in respiratory drive in response to a rise in arterial

carbon dioxide (PaCO2), thus maintaining PaCO2 within a narrow range. Patients with HF and

CSA tend to have an exaggerated respiratory response to carbon dioxide , associated with

excess sympathetic nervous activity, so that modest rises in PaCO2 that may occur during

sleep result in inappropriate hyperventilation (9,10). This drives the PaCO2 below the

“apnoeic threshold”, at which point the neural drive to respire is too low to stimulate effective

inspiration and an apnoea (complete pause in breathing) or hypopnoea (partial reduction in

airflow) ensues. PaCO2 subsequently rises and the cycle is repeated. This overshoot of the

homeostatic feedback loop is exacerbated by the prolonged circulation time between the

alveoli and the brainstem seen in more severe HF, so that the PaCO2 sensed in the brainstem

may not accurately reflect the PaCO2 at the lung. CSA is associated with increased

sympathetic nervous activity, more severe cardiac dysfunction, and lower resting PaCO2 (11).

The more prolonged the circulation time, the longer the duration of the hyperpnoeic phase of

CSA (12). In addition, pulmonary congestion and oedema lead to stimulation of J receptors in

the lungs, triggering reflex hyperventilation. A tendency to progress from OSA to CSA over

the course of the night has been observed, thought to be secondary to progressive pulmonary

congestion and deteriorating haemodynamics, which may itself be exacerbated by the SDB

(11). Typically cyclical ‘waxing and waning’ CSA is termed Cheyne-Stokes respiration.

Apnoea is currently defined as a reduction in airflow by at least 90% of pre-event baseline for

at least 10 seconds; hypopnoea as a reduction in airflow by at least 30% from baseline for at

least 10 seconds, associated with a fall in arterial oxygen saturation of at least 3%, or an

arousal from sleep (13). In OSA, there is evidence of on-going respiratory effort throughout

the apnoeic-hypopnoeic event, often with paradoxical movement of the chest and abdomen as

breathing against a closed airway is attempted. In contrast, apnoeas and hypopnoeas in CSA

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are accompanied by a marked reduction or cessation of respiratory effort. (Figure 1). The

average number of apnoeic and hypopnoeic events per hour of sleep is termed the ‘apnoea-

hypopnoea index’ (AHI). Up to 5 events/hour is defined as ‘normal’, 5-15/hour ‘mild’, 15-30

‘moderate’ and >30/hour ‘severe’ SDB. Those in whom >50% of events are obstructive are

labelled as ‘predominantly’ OSA, and if >50% of events are central such a patient is labelled

as ‘predominantly’ CSA.

Pathophysiological consequences of sleep-disordered breathing in heart failure

OSA may accelerate the progression of HF in several ways (Figure 2). The negative

intrathoracic pressure generated by the respiratory muscles trying to inspire against a closed

airway increases venous return to the right heart, increasing pre-load and causing the septum

to shift to the left which may compromise left ventricular (LV) function. The ability of the

failing LV to cope with enhanced pre-load is further impaired by the increased trans-mural

pressure during episodes of negative intrathoracic pressure, which increases the afterload.

Apnoea and hypopnoea activate the sympathetic nervous system – serum catecholamines and

muscle sympathetic nerve activity are higher in those with OSA and HF than matched

controls with HF only (10,14). Patients with OSA experience swings in blood pressure and

heart rate, which affects shear stress on the vascular endothelium and, in combination with

recurrent hypoxaemia, may lead to endothelial dysfunction - increased expression of the

vasoconstrictor endothelin-1 and a blunted response to cholinergic vasodilators have been

reported (15). The consequent vasoconstriction, hypertension and changes in protein

regulation and fibrosis in the myocardium may adversely affect left ventricular diastolic

function (16). Other changes associated with OSA are an increase in circulating C-reactive

protein concentration and enhanced platelet aggregation (17,18).

In contrast to OSA, CSA is typically considered a consequence rather than a cause of HF

(19). However, while those with CSA do not experience such marked episodes of negative

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intrathoracic pressure as seen in OSA, diurnal sympathetic activation is higher in those with

HF and CSA than matched controls with HF only (10). Just as in OSA, episodes of apnoea or

hypopnoea in CSA are associated with oscillations in heart rate, blood pressure, hypoxaemia

and possibly endothelial stress. C-reactive protein concentrations, known to be associated

with vascular events, are also elevated in those with CSA (20).

Both forms of SDB appear to be associated with an increase in sympathetic activity and this is

likely to be harmful – leading to additional peripheral vasoconstriction, tachycardia and renin-

angiotensin-aldosterone system stimulation with salt and water retention. In the

neurohormonal model of heart failure, damping of this response is considered vital to

improving the longer-term prognosis. Therefore SDB may be a new therapeutic target in heart

failure – additional to the effects of neurohormonal modulators such as beta-blockers,

angiotensin converting enzyme inhibitors and aldosterone antagonists.

Patients with SDB are at increased risk of malignant ventricular arrhythmia (21). Those with

OSA are most likely to receive ICD therapies at night (hazard ratio (HR) for appropriate

overnight ICD therapies 3.0 [CI 1.28-7.06, p=0.03] for those with moderate to severe OSA

relative to daytime risk), whilst those with CSA or no SDB are more likely to experience

appropriate ICD therapies during the day (22). Enhanced sympathetic activity, alongside

changes in intrathoracic pressure and haemodynamic disturbances, are thought to contribute

to this.

The effect of SDB on clinical outcomes in HF

Given the pathophysiological consequences of SDB, it is perhaps unsurprising that SDB is

linked to poor outcomes in those with HF and in the general population. The Sleep Heart

Health study followed 4422 patients free of heart disease at baseline for almost 9 years (23).

Those with severe OSA had more than twice the all-cause mortality during follow-up.

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However, severe OSA was found to be associated with an increased risk of coronary events

only in men less than 70 years of age. OSA was also associated with a 58% increase in risk of

developing HF de novo in men, but not women. In another study, only those with OSA and

HF of ischaemic aetiology were at increased risk of death over a mean follow up of 32

months (HR 3.03, CI 1.04-8.84, p=0.043), possibly related to the vascular stress induced by

OSA (24). Hypertension is also common amongst those with OSA, with absent nocturnal

dipping a frequent feature. Despite this, the high prevalence of confounding factors such as

obesity and metabolic syndrome in those with OSA has made proving a causal relationship

difficult (25).

CSA is also a marker of poor prognosis in HF – in one study mean survival for those with at

least moderate systolic dysfunction and CSA (mean AHI 34/hr) was 45 months vs. 90 months

for those without CSA (AHI<5/hr, p=0.02), a difference that persisted when adjusted for other

measured variables, including ejection fraction (26). However, the results of the SERVE-HF

randomised trial (27), in which effective treatment of CSA with adaptive servoventilation

(ASV) was associated with an increase in mortality, primarily driven by an increase in sudden

cardiac death, raise the possibility that CSA is either merely a marker of severity in HF, or

that it may be at least partially adaptive, as has been suggested by Naughton (28). During

hyperventilation, end-tidal volume increases by 400ml on average (29). This provides a

reservoir of oxygen in the lungs, which may counteract hypoxaemia in the presence of

pulmonary oedema and impaired gas exchange and expands the lungs to improve compliance

in a similar manner to CPAP therapy. The hyperventilation phase of CSA is also associated

with reduced sympathetic and increased vagal tone (30). In addition, episodes of

hyperventilation induce a respiratory alkalosis with hypocapnia, and this may help preserve

cardiac function during hypoxaemia (31). According to the Bohr and Haldane effects,

hypocapnia and alkalosis also increase the affinity of haemoglobin for oxygen, which may be

beneficial in the presence of pulmonary oedema and the acidosis commonly found in

decompensated HF. Swings in intra-thoracic pressure with hyper- and hypoventilation may

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have additional pump-like effects on the circulation. Oedema-induced bronchoconstriction

may also be partially reversed by hyperventilation (32). Recurrent episodes of hypoxaemia

may stimulate erythropoiesis and it is postulated that alternating high and low workload may

reduce respiratory muscle fatigue and improve oxygenation compared with constant effort

(33). If these effects are indeed protective, this could be a possible explanation for the

increased mortality reported in the SERVE-HF study (27). Others have disputed such an

explanation (34).

Diagnosing sleep-disordered breathing

Patients with HF and SDB do not tend to complain of daytime somnolence, possibly related

to the high sympathetic tone in heart failure. Screening questionnaires that include questions

about daytime sleepiness (such as the Epworth Sleepiness Scale used to screen for OSA in

non-heart failure populations) are therefore not useful (35). Attended in-hospital

polysomnography (PSG), including assessment of respiratory movement, oxygen saturation,

nasal and oral airflow, snoring, electroencephalography, electrocardiography,

electromyography and ocular movement, has long been considered the gold standard test for

sleep disorders. Whilst this provides comprehensive data, it is expensive, laborious and not

available in all centres. More limited, multi-channel sleep polygraphy (PG, with oxygen

saturation, nasal airflow, and chest and abdominal movement recorded) is more widely

available and can be set-up by the patient at home. It is comfortable to wear, less expensive

than in-hospital PSG, and the data produced are relatively simple to analyse. Studies

comparing the diagnostic accuracy of home polygraphy with PSG have shown that PG has a

sensitivity and specificity of 90-100% for the diagnosis of significant SDB (36,37). However,

an advantage of polysomnography is that periods of wakefulness are easily identified and

therefore AHI can be recorded during sleep only, whereas in polygraphy AHI is calculated

throughout the recording period regardless of sleep pattern and this may lead to an

underestimation of the severity of the SDB. Night-to-night variability in AHI is minimal in

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most patients with SDB and HF and a single night study is likely to produce a reliable

diagnosis (38).

Even simpler screening for SDB may be performed by recording nocturnal oxygen saturation

via a finger probe. For the diagnosis of moderate-to-severe SDB, Ward and colleagues have

reported a sensitivity of 93% and specificity of 73% compared to PSG when using a cut-off of

12.5 desaturations of at least 3% per hour, implying that few patients with clinically important

SDB would be missed by this simple approach (39). Nocturnal heart rate variability, whether

on a 24 hour tape or from an implanted device, reflects autonomic tone but does not appear to

be a useful approach to screening, although more sophisticated analytical algorithms show

promise (40). Whilst oxygen saturation monitoring is a simple and inexpensive method for

screening for SDB in heart failure, it cannot determine the phenotype of SDB and further

investigation with (at least) PG is mandatory in those who test positive, and in anyone who

tests negative but where clinical suspicion remains high.

Based on the high prevalence of SDB in HF and the current evidence on diagnostic testing, a

pragmatic approach might be to screen patients with HF with overnight pulse oximetry,

reserving PG or PSG for those with an oxygen desaturation index of > 12.5 events per hour

or a high pre-test probability based on clinical history (Figure 3).

In the past 10 years, there has been increasing interest in whether pacemaker algorithms could

be developed to accurately detect and quantify SDB (41). It is possible to continually measure

thoracic impedance between the right ventricular lead tip and the generator. On inspiration,

the increased volume of air in the chest increases thoracic impedance with the inverse

occurring on expiration, with consequent proportional changes in detected potential

difference. SDB diagnostic algorithms are now commercially available in certain pacemakers.

The DREAM study reported a sensitivity of 88.9% and specificity of 84.6% for the diagnosis

of moderate to severe SDB (42). Studies on other device platforms are currently underway

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(including NCT02204865). With the additional facility to download implanted device data

remotely, it is hoped that changes in SDB severity may be useful as an early marker of HF

decompensation, providing a window of opportunity to optimise treatment. Further research is

required.

Treatment options for patients with SDB and heart failure

Obstructive Sleep Apnoea

Continuous positive airway pressure (CPAP) is well-established in clinical guidelines for the

treatment of symptomatic OSA in the non-heart failure population (43). CPAP provides

continuous pressure (typically 5-10cmH20) throughout the respiratory cycle. The resultant

positive pressure prevents the pharynx from collapsing and thus reduces apnoea and

hypopnoea. It may have additional benefits in HF, as positive end-expiratory pressure

prevents alveoli collapsing secondary to pulmonary oedema and maintains alveoli at a greater

diameter, thus reducing the work of breathing. It also increases alveolar recruitment, improves

gas exchange and reduces right to left intrapulmonary shunting of blood. The positive

intrathoracic pressure reduces venous return (pre-load) and LV trans-mural pressure

(afterload) and may therefore benefit cardiac function in some patients.

There have been many studies of CPAP for OSA, with some studies examining HF

specifically. CPAP improves daytime somnolence, some measures of quality of life and

physical vitality scores (44). In a randomised control trial of 55 patients with HF and OSA,

nocturnal CPAP for 3 months improved LV ejection fraction (by 5.0±1.0% vs. 1.0±1.4%,

p=0.04) and reduced urinary noradrenalin excretion (45). Kaneko and colleagues

demonstrated that even one night of CPAP lowers systolic blood pressure (126±6 to

116±5mmHg, p=0.02), reduces heart rate (68±3 to 64±3/min, p=0.007) and improves LV end-

systolic diameter (54.5±1.8 to 51.7±1.2mm, p=0.009) in those with OSA and HF, compared

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to standard medical therapy (46). Another study with echocardiographic and cardiac magnetic

resonance follow-up demonstrated that CPAP improves right ventricular function, left

ventricular mass and pulmonary hypertension after 3 months of treatment. These

improvements persisted at 1 year (47). An observational study (88 patients) of CPAP versus

medical therapy for those with HF and moderate to severe OSA demonstrated a significantly

higher rate of hospitalisation or death in the non-CPAP group (HR 2.03, CI 1.07 to 3.68,

p=0.03) compared to those treated with CPAP (48). Patients who were not compliant with

CPAP also had a higher risk of the composite endpoint. Two other large registry studies

found similar results (49,50). Perhaps because of the lack of appropriately-sized randomised

outcome studies, no international heart failure guidelines yet exist for the use of CPAP in

patients with HF and OSA in the absence of daytime somnolence. The effect of CPAP on

hypertension, stroke and myocardial infarction risk is debated and beyond the scope of this

review.

Therapy with continuous nocturnal oxygen has been used in those intolerant of CPAP. A

meta-analysis of 14 studies concluded that oxygen therapy does reduce overnight

desaturations, but prolongs apnoeas and hypopnoeas (51). CPAP was shown to be superior to

oxygen in reducing AHI in OSA and the effect of oxygen on prognosis in OSA is not known.

More generally, optimisation of HF therapy improves cardiac output and reduces peripheral

oedema, presumably minimising rostral fluid shift and pharyngeal oedema. The impact on

AHI is unknown. Weight loss significantly reduces AHI in obese patients with OSA. Meta-

analysis of seven randomised controlled trials shows that weight loss programmes result in a

mean reduction in AHI of 6.04 events/h (CI -11.18 to -0.90) (52). However, patients with HF

and OSA are less likely to be obese and the impact in this group is not known. In patients

with retrognathism, mandibular advancement devices may also significantly improve AHI in

OSA (53).

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Central Sleep Apnoea

The optimal management of CSA in HF is less well determined than OSA. Medical therapy

with acetazolamide has been reported to reduce AHI, which may be due its respiratory

stimulating properties as well as a diuretic action (54). Whether furosemide achieves the same

effect is unknown, although reduction in pulmonary congestion might be expected to lessen

CSA by reducing pulmonary J-receptor stimulation. Cardiac resynchronisation therapy (CRT)

significantly reduces AHI in CSA with HF (55). Meta-analysis of trials investigating the

effect of CRT on CSA reports a mean reduction in AHI of 13.05/h (CI −16.74 to −9.36;

p<0.00001), whereas CRT has no effect on AHI in patients with predominantly OSA (56).

Nocturnal oxygen therapy has been shown to reduce sympathetic drive and increase nocturnal

oxygen saturation in CSA and HF (57). The CHF-HOT trials randomised a small number of

patients with CSA and HF to standard medical therapy with or without home oxygen therapy.

Meta-analysis of the results from 97 patients, demonstrated a decrease in AHI (−11.4 ± 11.0

vs. −0.2 ± 7.6/h, p<0.01) and an improvement in LV ejection fraction (36.1 ± 11.8 to 46.3 ±

16.2% p=0.014) in those with severe CSA (58) treated with home oxygen at 3l/min via an

oxygen concentrator, at least out to 12 weeks. There was also an improvement in mean New

York Heart Association (NYHA) Class, but no overall improvement in ventricular ectopy or

plasma catecholamine concentrations. The impact on prognosis is unknown.

Early small trials of CPAP in CSA with HF demonstrated an improvement in AHI, reduced

daytime natriuretic peptide and catecholamine plasma concentrations and improved LV

ejection fraction and in one small study of 29 patients there was a trend towards improved

survival with CPAP (59). A larger randomised controlled trial (the CANPAP study) was

designed to evaluate the effect of CPAP on transplant-free survival in patients with CSA and

HF (60). This trial was stopped early after 258 patients had been randomised and followed up

for over 2 years: there was no difference in transplant-free survival between CPAP and the

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optimal medical therapy alone arm. CPAP did result in an improved AHI (-21±16 vs.

–2±18/hr, p<0.001), LV ejection fraction (2.2±5.4% vs. 0.4±5.3%, p=0.02), 6-minute walk

test distance and reduced plasma noradrenaline concentrations, but this did not translate into a

survival advantage. Post-hoc subgroup analysis suggested that there was a survival advantage

in those in whom the AHI was supressed by the CPAP therapy to below 15/hr, suggesting a

possible role for more efficacious ventilatory techniques, such as adaptive servoventilation

(ASV) (61).

Adaptive servo-ventilation (ASV) is a more sophisticated mode of non-invasive ventilation in

which the ventilator increases inspiratory support during hypopnoea, withdraws support

during hyperventilation, provides mandatory breaths during apnoea and generates background

positive airways pressure. It is therefore effective in both CSA and OSA. Teschler and

colleagues showed that ASV is more effective than CPAP or oxygen therapy in suppressing

CSA events and is better tolerated by patients than CPAP (Figure 4) (62). Meta-analysis of

trials on ASV in CSA and HF to date suggested an overall improvement in AHI (-14.64/hr; CI

-21.03 to -8.25), as well as improvements in LV ejection fraction, diastolic dimensions and

function, 6-minute walk test distance, plasma BNP concentration and sympathetic activity

(63–65).

Given these beneficial effects, a large randomised controlled trial, SERVE-HF, was

undertaken to assess the impact of ASV on hospitalisation, life-saving cardiovascular

intervention or death in those with HF and CSA (27). 1325 patients with a LV ejection

fraction of 45% or less and moderate-to-severe (predominantly) CSA were enrolled. At 12

months, ASV was highly efficacious at reducing AHI (from a mean of 31.2 events per hour at

baseline to 6.6 per hour). Despite the good control of the CSA, there was no difference in the

primary endpoint (of all-cause mortality, unplanned HF hospitalisation or life-saving

cardiovascular intervention) between the two groups, and a higher overall mortality and

cardiovascular mortality in those treated with ASV (HR for all-cause mortality, 1.28; 95% CI,

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1.06 to 1.55; p = 0.01; and HR for cardiovascular mortality 1.34; 95% CI, 1.09 to 1.65; p =

0.006). This trial did not find differences plasma BNP concentration, 6-minute walk test or

health related quality of life between the two randomised groups. Further analyses of the

mode of death and data from the patients who had an implanted device with defibrillator

capacity are awaited, but initial results suggest that the excess mortality is driven by an

increase in sudden death. There was no difference in deaths from pump failure or admissions

to hospital with heart failure decompensation. Various explanation have been proposed:

chance, a direct toxic effect of PAP on patients with poor LV function and a low pulmonary

capillary wedge pressure, or that CSA may be at least partially adaptive for patients with

severe heart failure. Further data will emerge from another randomised trial of an ASV device

in patients with heart failure and reduced ejection fraction and either predominantly OSA or

CSA (ADVENT-HF; NCT01128816).

CSA is found in the majority of patients with acute decompensated (as opposed to chronic)

HF, is usually severe and is associated with an increased risk of readmission and mortality

(66). A randomized trial of ASV in this patient group was initiated, but was terminated after

the results of SERVE-HF became available. (CAT-HF; NCT01953874).

A novel therapy for pure CSA currently under evaluation is the phrenic nerve stimulator

(Remede©, Respicardia, USA). This device is similar to a pacemaker, with an electrode that

stimulates the phrenic nerve via the left pericardiophrenic or right brachiocephalic vein. It can

be implanted percutaneously under sedation in the catheter laboratory. The device unilaterally

stimulates the phrenic nerve when no impulse is sensed for a pre-determined time period,

inducing a breath. A non-randomised study of 57 patients showed a mean reduction of 55% in

AHI over 3 months (49.5±14.6/h to 22.4±13.6/h, p < 0.0001) as well as reductions in

arousals, oxygen desaturation index and improved quality of life indices (67). Device or

procedure-related adverse events occurred in 26% of patients, predominantly due to lead

displacement. A somewhat larger randomized study has completed recruitment to further

14

evaluate the effect of this technology on the reduction in CSA events but is not powered to

determine the effect on hospitalization or mortality (NCT01816776). For those with OSA, a

similar device exists which stimulates the hypoglossal nerve in response to apnoea and

hypopnoea. An uncontrolled study has shown a significant mean reduction of 68% in AHI

over 12 months in those treated with this stimulator (68). The impact on cardiovascular

outcomes is not known.

Compliance with Positive Airway Pressure Therapy

An important part of positive airway pressure therapy is the delivery interface: nasal pillows,

nasal mask, or oronasal mask. These should be chosen depending on the patient’s facial

features and preferences, and are best dealt with by a service used to setting up patients so any

early problems are resolved rapidly. For all therapies, current targets are to control SDB so

that the AHI is below 5/hr. Experience in our unit is that 80% of heart failure patients are able

to comply with long-term mask therapy if they are aware of the rationale for treatment, and

they are supported through the first few weeks of treatment. Ideally, the cardiologist should

work with the respiratory or sleep physician to ensure a consistent approach to diagnosis and

treatment.

Conclusions

SDB is found in at least half of patients with HF, and is associated with a worse prognosis.

Pathophysiological abnormalities found in SDB (both obstructive and central types) include

cyclical activation of the sympathetic nervous system and periodic hypoxaemia, which may

accelerate cardiac deterioration and trigger arrhythmia. In-hospital PSG is the current

diagnostic gold standard, but simple screening tests such as overnight oximetry or at-home

PG can easily identify patients with a high probability of SDB. Treatment of OSA with CPAP

improves markers of cardiovascular function and there are observational data suggesting a

survival benefit, but a lack of data from an appropriately sized randomized trial with mortality

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and morbidity outcomes. The optimal treatment of CSA remains uncertain and PAP cannot be

recommended on current evidence. Further research is needed to determine whether CSA is

merely an epiphenomenon, is partially adaptive, or is a risk factor for poor outcome that

requires diagnosis and treatment.

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Figures

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Figure 1.

Fig. 1a. Severe obstructive sleep apnoea on sleep polygraphy. Note the persistence of

respiratory effort during apnoeas and the marked swings in heart rate and oxygen saturation.

Fig. 1b. Severe central sleep apnoea on sleep polygraphy. Note the absence of respiratory

effort during apnoeas.

Figure 2.

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The interplay between sleep-disordered breathing and heart failure. (CSA - central sleep

apnoea, OSA - obstructive sleep apnoea). Reprinted from Brenner S, Angermann C, Berthold

J, Ertl G, Stork S. Sleep-disordered breathing and heart failure: a dangerous liaison. Trends

Cardiovasc Med 2008;18:240–247. Copyright © 2008 with permission from Elsevier.

Figure 3.

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Suggested flow chart for the investigation of sleep-disordered breathing in heart failure. AHI -

apnoea-hypopnoea index, CSA - central sleep apnoea, OSA - obstructive sleep apnoea, HF

heart failure, PAP - positive airway pressure.

Fig 4.

The effect of different modes of non-invasive ventilation on central apnoea index. Horizontal

bar: median; thick vertical line: interquartile range; circles: outliers; thin bar: range excluding

outliers. CPAP – continuous positive airway pressure, ASV – adaptive servoventilation.

Reprinted with permission of the American thoracic society. Copyright © 2015 American

Thoracic Society. Teschler H, Dohring J, Wang YM, Berthon-Jones M. Adaptive pressure

support servoventilation: A novel treatment for Cheyne-Stokes respiration in heart failure.

Am J Resp Crit Care 2001;164:614-619. The American Journal of Respiratory and Critical

Care Medicine is an official journal of the American Thoracic Society.

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