PFO Closure for Obstructive Sleep Apnoea
PFO Closure for Obstructive Sleep Apnoea
Obstructive sleep apnoea (OSA) is a condition which involves episodes of interrupted
 breathing during sleep due to repetitive narrowing or collapse of the throat. These episodes
 are usually associated with a drop in blood oxygen levels and brief awakenings, which disrupt
 the sleep of those affected and can lead to daytime sleepiness. OSA is associated with an
 increased risk of heart disease and stroke.

 In some individuals, the low oxygen levels in the blood can be made worse by also having a
 small hole in the heart, called a patent foramen ovale (PFO). This hole is present at birth
 in everyone, but in some people (about 30% of the normal population) it fails to close.
 Usually a PFO does not cause any medical problems. However, it may be recommended to have a
 PFO closed by key-hole surgery if someone suffers a stroke, severe migraine or if they are
 professional divers. There is a higher incidence of PFO in patients with OSA (25-50%)
 compared to the wider population and this may account for some of the observed increased risk
 of heart disease and stroke in patients with OSA.

 This study will assess the number of patients with OSA who also have a PFO, and whether
 closing the PFO can improve the symptoms of OSA (e.g. sleepiness, exercise capacity and
 general well-being), thereby enabling the patient to not be reliant on treatment for OSA. If
 the study shows that closing the PFO is beneficial then the investigators will assess in a
 larger study if this treatment can also reduce heart disease and strokes.
Under normal conditions an interatrial communication allows blood to shunt from left to right
 due to a higher pressure in the left atrium than the right atrium and a greater compliance of
 the right ventricle than the left ventricle. Right-to-left interatrial shunting (RLS) is
 usually associated with spontaneous or induced pulmonary hypertension. RLS may occur
 spontaneously during a release phase of a Valsalva manoeuvres that transiently generates a
 right to left pressure gradient across the interatrial septum or rarely due to a condition
 termed platypnea-orthodeoxia. The latter is characterized by dyspnoea and deoxygenation
 accompanying a change to a sitting or standing from a recumbent position.
 Platypnea-orthodeoxia is thought to be due to a combination of an interatrial communication
 and an anatomical variant e.g. a persistent Eustachian valve and/or stretching and distortion
 of atrial septum allowing more streaming of venous blood from inferior vena cava through the
 defect when in the upright position. The recommended treatment of platypnea-orthodeoxia is
 percutaneous closure of patent foramen ovale (PFO).

 Obstructive Sleep Apnoea - Hypopnoea Syndrome (OSAHS) is characterised by repetitive upper
 airway obstruction during sleep causing apnoea (cessation of breathing) and oxygen
 desaturation. It is a significant health burden on the National Health Service (NHS) and
 society, affecting approximately 4% middle aged men and 2% middle-aged women. The risk of
 OSAHS rises with increasing body weight, active smoking and age. OSAHS is set to reach
 epidemic proportions as the Western population ages and the incidence of obesity rises. About
 1% of men in the United Kingdom (UK) have severe OSAHS with an apnoea-hypopnoea index (AHI;
 the average number of episodes of apnoeas and hypopnoeas per hour of sleep) of >20 and oxygen
 desaturation index (ODI; the number of desaturation episodes defined as ≥4% drop in oxygen
 saturations per hour during sleep) of >20, measured by nocturnal oximetry and respiratory
 polygraphy (intermediate sleep study or Embletta™). Patients with untreated severe OSAHS have
 a higher incidence of fatal (OR 2.87) and non-fatal (OR 3.17) cardiovascular events compared
 to age and sex matched controls. The degree of oxygen desaturation inversely correlates with
 survival and the link is thought to be multifactorial; raised blood viscosity due to
 increased haematocrit, sympathetic activation leading to arrhythmias and systemic
 hypertension are thought to be important. In a Cox model a 1% decrease in average nocturnal
 oxygen saturation (SaO2) was associated with a 33% increase in the incident risk of fatal and
 nonfatal cardiovascular events. Treatment with continuous positive airways pressure (CPAP)
 ventilation at night reduces symptoms (snoring, mood, day time sleepiness and headache) and
 cardiovascular event rate, but it is poorly tolerated and refused by up to a fifth of
 patients. Improvement in ODI and sleepiness in OSAHS treated by CPAP is transient and when
 CPAP is discontinued, measurements return to baseline within 1 week.

 PFO is found with a higher incidence in patients with OSAHS than controls (69% vs. 17%) and
 may exacerbate the oxygen desaturation in OSAHS during apnoeic/ hypopnoeic episodes observed
 in some patients. In OSAHS patients with greater ODI to AHI ratio (ODI/AHI>0.67), the
 prevalence of large PFO was nine out of 15 (60%) versus two out of 15 (13%) in those with
 ODI/AHI <0.33. OSAHS is believed to raise right heart pressures and increase RLS via the
 interatrial defect due to repeated nocturnal Valsalva and Muller manoeuvres. Prolonged oxygen
 desaturation may further exacerbate sleep apnoea by decreasing central respiratory drive. In
 selected populations of OSAHS patients, PFO closure may be beneficial. This has been reported
 in a number of case reports but has not been studied in a larger trial population.

 Hypothesis:

 RLS via a PFO in patients with severe OSAHS: ESS≥11 and ODI≥20 or ODI/AHI >0.67, is
 deleterious and closing the PFO will improve oxygen saturation, exercise tolerance, symptoms,
 quality of life and will reduce CPAP requirement and, ultimately, will reduce the incidence
 of fatal/ non-fatal cardiovascular events.

 This study will assess the improvement of symptoms of OSA (e.g. sleepiness, exercise capacity
 and general well-being) following PFO closure. Improving symptoms will enable patients to not
 be reliant on treatment for OSA. If PFO closure is beneficial the investigator aims to assess
 the efficacy of treatment to reduce heart disease and strokes in a larger study.
Inclusion Criteria:

 -  Age 18 years and older

 -  Diagnosis of obstructive sleep apnoea-hypopnoea syndrome (OSAHS)

 -  Epworth Sleepiness Scale score of 11 or greater

 -  Oxygen Desaturation Index of 20 or greater (and/or oxygen desaturation
 index/apnoea-hypopnoea index greater than 0.67)

 -  Naive to Continuous Positive Airway Pressure (CPAP) treatment, or CPAP intolerant
 (defined at any review as: CPAP use less than 4 hours per night and unable to
 tolerate/receive no benefit, or at clinical discretion), or poor CPAP responders
 (defined at any review as: failure to improve Epworth Sleepiness Scale score by more
 than 4 points from Epworth Sleepiness Scale score at diagnostic visit plus persistent
 symptoms suggesting poorly controlled OSAHS and/or a prior failure to tolerate CPAP
 therapy)

 -  Moderate to large Patent Foramen Ovale (PFO) as seen on a transthoracic echocardiogram
 bubble study

 CPAP naive patients with moderate-large PFO will start CPAP treatment during the study, but
 outcomes will be assessed at baseline (before starting CPAP treatment) and at six months
 post PFO closure (after one week of CPAP abstinence).

 Exclusion Criteria:

 -  Coexistent significant respiratory disease (FEV1 <50% predicted)

 -  Weight >180kg (maximum weight allowance for echocardiogram table)

 -  Known or suspected pregnancy

 -  Other cardiac disease (valve disease, known cardiomyopathy, left ventricular failure,
 known congenital heart disease)

 -  Previous atrial septal closure device

 -  Inability to give informed consent or comply with the protocol

 -  Anatomically unsuitable for percutaneous PFO closure with Gore™ septal occluder
 device.