Obstructive Sleep Apnoea
Positive airway pressure (PAP) therapy delivered through a nasal (or nasal-oral) mask stabilises the airway (preventing collapse) and is the standard treatment for SDB associated with daytime sleepiness in the non-HF population [
70,
71]. There are a variety of different treatment modalities, including continuous positive airway pressure (CPAP) therapy [
72].
An overnight PAP titration study is required to determine the optimal pressure setting that reduces the number of apnoeas/hypopnoeas during sleep, improves hypoxaemia and sleep architecture, and reduces arousals. Potential beneficial cardiovascular effects of CPAP therapy include increased intrathoracic pressure, reduced LV preload and afterload, and reduced transmural cardiac pressure gradients, all of which can ameliorate impaired cardiac function. CPAP therapy improves daytime somnolence and some measures of quality of life and physical vitality scores in patients with OSA but without HF [
73].
Adherence with this therapy is highly variable, with average levels ranging from 50 to 80 %, but with around 70 % still regularly using treatment after 5 years [
74]. Adherence is positively influenced by patient education, careful selection of a mask that best fits the patient, and supportive management of nasal congestion or dryness.
In a randomised control trial of 55 patients with HF and OSA, nocturnal CPAP therapy 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 [
75]. Even one night of CPAP therapy lowers systolic blood pressure (126 ± 6 to 116 ± 5 mmHg,
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 ± 1.2 mm,
p = 0.009) in those with OSA and HF, compared to standard medical therapy [
76]. CPAP therapy improves right ventricular function, left ventricular mass, and pulmonary hypertension after 3 months of treatment, and these improvements persisted at 1 year [
77]. An observational study (88 patients) of CPAP therapy 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 therapy group (HR 2.03, CI 1.07 to 3.68,
p = 0.03) compared to those treated with CPAP therapy [
78]. Patients who were not compliant with CPAP therapy also had a higher risk of the composite endpoint. Two other large registry studies found similar results [
79,
80].
The 2010 Heart Failure Society of America Comprehensive Heart Failure guidelines recommend screening for SDB and CPAP therapy in those with confirmed OSA [
81]. The 2013 ACCF/AHA guidelines states that treating OSA with CPAP therapy in patients with HF does have benefit [
82].
Further data will emerge from a randomised trial of adaptive servoventilation device in patients with heart failure and reduced ejection fraction and either predominantly OSA or CSA (ADVENT-HF; NCT01128816), which is currently recruiting patients.
Central Sleep Apnoea
A number of treatments for CSA/CSR have been studied, including oxygen, carbon dioxide, CPAP therapy, and adaptive servoventilation (ASV).
Although it does not trigger inspiration during central apnoea, CPAP therapy improves CSA/CSR probably by increasing functional residual capacity (and, as a result, oxygen stores), decreasing blood volume in the lungs and upper airway when lying down, and reducing hyperventilation via a direct effect on the parabasal J receptors of the lung. In addition, CPAP therapy reduces preload and afterload and the cardiac transmural pressure and may benefit cardiac function in some patients.
Early small trials of CPAP therapy in CSA with HF demonstrated an improvement in AHI, reduced daytime plasma natriuretic peptide and catecholamine concentrations, and improved LV ejection fraction. A larger randomised controlled trial (the CANPAP study) was designed to evaluate the effect of CPAP therapy on transplant-free survival in patients with CSA and HF [
83]. 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 therapy and the optimal medical therapy alone arm. CPAP therapy improved the AHI (−21 ± 16 vs. –2 ± 18/h,
p < 0.001), LV ejection fraction (2.2 ± 5.4 vs. 0.4 ± 5.3 %,
p = 0.02), and 6-min walk test distance and reduced plasma noradrenaline concentrations, but this did not translate into improved survival. Post hoc subgroup analysis suggested that there was a survival advantage in those in whom the AHI was suppressed by CPAP therapy to below 15/h, suggesting a possible role for more efficacious ventilatory techniques, such as ASV [
84].
ASV has been shown to be the most effective mask-based intervention for controlling (central) SDB in patients with HF [
85]. ASV increases inspiratory support during hypopnoea, withdraws support during hyperventilation, provides mandatory breaths during apnoea, and generates background PAP. It is therefore effective in both CSA and OSA and can suppress complex sleep apnoea [
86].
In small randomised clinical trials, beneficial effects of ASV treatment of CSA/CSR in HF patients include significant reductions in AHI, N-terminal pro-B-type natriuretic peptide (BNP) concentrations, urinary catecholamine release, and LV end-systolic diameter; increases in 6-min walk distance and LV ejection fraction; and improved New York Heart Association (NYHA) class [
87,
88].
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 [
89•]. One thousand three hundred twenty-five patients with a LV ejection fraction ≤45 % and moderate-to-severe (predominantly) CSA were enrolled. At 12 months, ASV was highly efficacious at reducing AHI (from a mean of 31.2/h at baseline to 6.6/h). Despite the good control of the CSA, there was no difference in the primary endpoint between the two groups, and there was a higher overall mortality in those treated with ASV (HR for all-cause mortality 1.28, 95 % CI 1.06 to 1.55,
p = 0.01; HR for cardiovascular mortality 1.34, 95 % CI 1.09 to 1.65,
p = 0.006). This trial did not find differences in plasma BNP concentration, 6-min walk test, or health-related quality of life between the two randomised groups. Initial results suggest that the excess mortality was driven by an increase in sudden death, with no difference in deaths from pump failure or admissions to hospital with HF decompensation. Various explanations 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 [
11]. Further data will emerge from the ADVENT-HF study (NT01128816). In the meantime, the use of ASV (or other airway pressure therapies) for the treatment of predominantly central sleep apnoea in HF patients with reduced ejection fraction cannot be recommended. For those already on ASV, they should be counselled about the potential risks of continuing with this therapy.
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 [
90]. A randomised trial of ASV in this patient group was initiated but was terminated after the results of SERVE-HF became available (CAT-HF; NCT01953874). The results have yet to be published.
Another area of interest is the use of ASV in patients with HFpEF and CSA/CSR. Early results suggest that ASV can improve cardiac diastolic function, improve symptoms, and decrease B-type natriuretic peptide concentrations in such patients [
91,
92]. In addition, the proportion of HFpEF patients treated with ASV who were free of cardiac events were significantly higher than those of untreated patients. No adequately powered randomised trial has been undertaken.