Patent Foramen Ovale Closure in the Treatment of Obstructive Sleep Apnea

ABSTRACT: Obstructive sleep apnea (OSA) and patent foramen ovale (PFO) are common conditions and may coexist. In patients with OSA, increases in right-to-left shunting across a PFO may result in increased burden of hypoxia, although the effect of this is unknown. We report the cases of 3 patients with highly symptomatic OSA and PFO who underwent percutaneous closure with the Coherex FlatStent PFO Closure System. Although PFO closure can be achieved with minimally invasive techniques and low rates of adverse events, its importance in reducing hypoxia in this population is unknown. PFO closure may result in improvement in apneas and symptoms in selected OSA patients and may impact cardiovascular events in this group through hypoxia-mediated or other unrecognized mechanisms.

J INVASIVE CARDIOL 2013;25(8):E169-E171

Key words: heart septal defects, obesity, sleep

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Obstructive sleep apnea (OSA) is a common disorder, affecting up to 24% of men and 9% of women in general population studies.1 It has been associated with a range of adverse cardiovascular events.^2-5 The prevalence of patent foramen ovale (PFO) in the general population is also high, affecting up to 27% of adults.6 Recent studies have drawn associations between OSA and PFO and demonstrated that PFO is more common in patients with OSA than normal controls.^7,8 Consequently, it appears that the prevalence of both conditions coexisting could be high. Recent reports have proposed that these conditions may influence each other’s pathophysiology and that PFO closure may provide a therapeutic option in reducing hypoxia and subsequent symptoms in OSA.^9,10

We report a case series of 3 patients with highly symptomatic OSA despite standard care who underwent percutaneous PFO closure. This small series comes from patients enrolled in an observational study designed to test the efficacy of PFO closure in OSA. The study was a multicenter, non-randomized cohort, intended to recruit up to 50 cases in 6 centers internationally. Patients with OSA and a polysomnogram (PSG) documenting an apnea index >20 seconds greater than 5 and oxygen desaturation index >10% greater than 5 were screened with an echocardiogram for PFO. The study included patients with a right-to-left shunt on transcranial Doppler (TCD) and a transesophageal echocardiogram (TEE) demonstrating PFO suitable for percutaneous closure who consented to undergo closure. The study was terminated due to slow recruitment, after enrollment of only 3 patients at our center. 

All patients underwent PFO closure with the Coherex FlatStent EF PFO Closure System (Coherex Medical), a 0.51-mm thick nitinol implant with microtined anchors that attach to the walls of the left and right atrium (Figure 1). The implant is unsheathed in the PFO tunnel where it expands laterally, apposing the walls of the septum primum and the septum secundum. The system is available in two sizes, 13 mm and 19 mm. The size designation indicates the width of the center portion of the device, which lies within the PFO tunnel.

Case 1. A 55-year-old man with no known medical problems presented with a 1-year history of daytime somnolence, morning headaches, and snoring. His body mass index (BMI) was 33 kg/m2 and his blood pressure was mildly elevated at 140/85 mm Hg. A split-night PSG showed moderate OSA with an apnea-hypopnea index (AHI) of 25/hour and an oxygen desaturation index ≥4% (ODI) of 38/hour. After a 6-month trial of continuous positive airway pressure (CPAP), his symptoms had not improved. An echocardiogram showed a PFO with a significant right-to-left shunt (Spencer grade 4) on TCD. In light of his persistent symptoms, he underwent PFO closure. At 6-month follow-up, he reported markedly improved sleep quality and resolution of his daytime somnolence and headaches. He no longer required CPAP and his blood pressure had improved to 120/85 mm Hg. Follow-up PSG showed a reduction in both AHI to 18/hour and ODI to 30/hour. TEE showed stable device appearances with no residual shunt by color Doppler and agitated saline contrast study.

Case 2. A 56-year-old man with a 4 year-history of OSA, already established on CPAP, was referred for consideration of PFO closure after echocardiographic diagnosis. He suffered from longstanding lethargy and daytime somnolence despite CPAP therapy. His BMI was 31 kg/m2 and blood pressure was 124/75 mm Hg. Prior to PFO closure, PSG showed moderate OSA with AHI 16/hour and ODI 41/hour. TCD confirmed a significant shunt (Spencer grade 4). At 3-month follow-up, despite stable TEE appearances of the closure device and no residual shunt, he reported no improvement in his symptoms and continued to require CPAP. Despite no change in symptoms, follow-up PSG showed a marked decrease in AHI to 0.3/hour and ODI to 8/hour. His blood pressure remained unchanged.

Case 3. A 36-year-old man with chronic sinusitis presented with unintentional weight gain, daytime somnolence, and witnessed apneas. His BMI was 38 kg/m2 and blood pressure was 120/84 mm Hg. An Epworth Sleepiness Score was 18/24 and PSG confirmed moderate OSA with AHI 11/hour and ODI 17/hour. He was established on CPAP but tolerated it poorly due to sinusitis and after he was found to have a PFO at echocardiogram, was referred for PFO closure. TCD showed a significant shunt (Spencer grade 4). At 3-month follow-up, TEE showed stable appearances of the closure device and no residual shunt. He remained unable to tolerate CPAP and experienced no change in his symptoms or blood pressure. Follow-up PSG showed a small decrease in AHI to 9/hour and ODI to 10/hour.

Discussion. The role of right-to-left shunting in the pathophysiology of OSA in patients with concomitant PFO is not well defined. Although PFO closure can be achieved with minimally invasive techniques and low rates of adverse events,¹² its importance in reducing hypoxia in this population is unknown. Even in the absence of elevated right heart pressures, transient right-to-left shunting across PFO is common¹³ and has been shown to be increased by obstructive apneas.¹⁴ The significant shifts in intrathoracic pressure seen in OSA result in alterations in venous return and where these occur in the presence of PFO, the altered interatrial pressure gradients might result in important volumes of deoxygenated right atrial blood being shunted across the interatrial septum, into the systemic circulation. It is possible that OSA patients with PFO might suffer more frequent desaturations than those with an intact interatrial septum.¹⁵ Hypoxia has been shown to cause pulmonary vasoconstriction and pulmonary hypertension,¹⁶ which can result in increased right ventricular afterload and right atrial pressure. This may increase right-to-left shunting further, creating a cycle of worsening hypoxia, pulmonary hypertension, and shunting. Furthermore, it may be that the increases in right heart pressures seen in OSA might favor the persistence, or reopening of, small PFOs that might otherwise have remained closed.

Although not proven, PFO closure in OSA has been previously described and might result in improved symptoms in selected patients.^9,10 This may have a role particularly in patients intolerant of standard care, including CPAP. Although we reported 1 case of dramatic symptomatic improvement following PFO closure, the mechanism by which this could occur remains unclear. It is usually considered that the symptoms of OSA are determined by nocturnal arousals, which disrupt sleep architecture, resulting in daytime somnolence and fatigue. However, hypercarbia and mechanical factors are recognized as the most important factors in precipitating arousal. By comparison, the role of hypoxia in stimulating arousal is inconsistent.¹⁷ So if PFO closure is presumed to improve symptoms, it is likely to be by a mechanism other than a reduction in hypoxic episodes. We report 3 cases with a reduction in apneas after PFO closure. While it seems feasible that PFO closure could reduce episodes of desaturation, the mechanism by which apneas could be reduced is not clear. Apneas are described as temporary reductions in airflow due to upper airway collapse, despite continued inspiratory effort.¹⁸ Transient hypoxia is the logical consequence, rather than cause, of this reduction in flow. That PFO closure should directly result in a reduction of apneas seems unlikely.

The increased cardiovascular risk associated with OSA is well recognized and it has been shown specifically that hypopneas are associated with systemic hypertension, pulmonary hypertension, arrhythmias, heart failure, and coronary disease in some populations.^2-5 However, no causal association between apneas, shunting, hypoxia, and cardiovascular events has been defined. So although PFO closure in OSA might reduce the severity of transient hypoxia, no specific role for device closure in order to reduce cardiovascular events exists based on current evidence. However, it is possible that unrecognized neurohumoral actors in shunted venous blood or factors produced in response to hypoxia might play a causal role in incident cardiovascular disease.

Conclusion. We report 3 cases of PFO closure for the treatment of OSA symptoms. Both PFO and OSA are common conditions and associated with increased cardiovascular morbidity. PFO closure might result in a significant improvement in apneas and symptoms in selected OSA patients and might impact cardiovascular events in this group through hypoxia-mediated or other unrecognized mechanisms.

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From the ¹Green Lane Cardiovascular Service, Auckland City Hospital and ²New Zealand Respiratory and Sleep Institute, Auckland, New Zealand.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted December 5, 2012, provisional acceptance given December 12, 2012, final version accepted February 11, 2013.

Address for correspondence: Dr Jonathon White, Green Lane Cardiovascular Service, Level 3, Auckland City Hospital, Private Bag 92024, Auckland 1030 New Zealand. Email: jonathonw@adhb.govt.nz