Improvement in pulmonary function following closure of a patent foramen ovale in a man with cystic fibrosis

Introduction

Patent foramen ovale (PFO) is a remnant of the fetal circulation and represents a failure of fusion of the primum and secundum septa during the postnatal period. ¹ Persistence of the one-way flap valve overlying the fossa ovalis allows right-to-left blood flow when right atrial pressure exceeds left atrial pressure. Within the general population PFOs are relatively common and are present in 27% of unselected adults. ² Little is known of the incidence of PFOs within the cystic fibrosis (CF) population and their impact on clinical outcomes. The present case report describes an adult CF patient who presented with neurological symptoms and deteriorating pulmonary function in the setting of a PFO. Closure of his PFO resulted not only in complete resolution of his neurological symptoms, but an improvement in pulmonary function.

DECLARATIONS

Competing interests

None declared

Funding

None

Ethical approval

Not applicable

Guarantors

MB

Contributorship

Both authors contributed equally

Case report

A 29-year-old man with cystic fibrosis presented complaining of ‘funny turns’ while performing his daily physiotherapy. He described numbness and tingling of the left arm and leg which was intermittently accompanied by weakness of these limbs. He also complained of fleeting episodes of visual loss and palpitations during these ‘funny turns’. The episodes would last up to 30 minutes and then subside spontaneously. These incidents were almost exclusively precipitated by forced expiratory manoeuvres and excessive coughing. At the time of presentation his FEV1 was 1.36 and FVC 3.45 (33% and 71% predicted) and had declined from a stable baseline of FEV1 1.7 and FVC of 4.1 (42% and 86% predicted).

The patient was diagnosed with cystic fibrosis at birth following failure to thrive. His genotype was identified as homozygous A508. He was found to be pancreatic insufficient at the time of diagnosis. His early childhood was largely uneventful until the age of 12 years when he was diagnosed with allergic bronchopulmonary aspergillosis which required prolonged treatment with oral corticosteroids. At 13 years he developed a vitreous abscess of left eye which required enucleation and insertion of a prosthesis. During the same year he sustained osteoporotic crush fractures of T9 and T10. The patient also became chronically colonized with Pseudomonas aeruginosa at this time. Following on from these events his symptoms were relatively stable and he required, on average, 1-2 courses of intravenous antibiotics per year. There were no new significant events until his presentation with ‘funny turns’.

A transthoracic echocardiogram demonstrated a patent foramen ovale with significant right-to-left interatrial shunt even without valsalva manoeuvre (Figures 1 and 2). The left- and right-sided chambers of his heart had normal dimensions and function, and no valvular abnormalities were identified. There was no evidence of intracardiac thrombus present. A thrombophilia screen and cranial MRI were unremarkable. The patient was commenced on aspirin therapy and taught to perform autogenic drainage physiotherapy. He also received a two-week course of intravenous antibiotics. His PFO was closed shortly afterwards by percutaneous insertion of an Amplatzer PFO occluder device. Following closure the patient has been able to re-introduce forced expiratory manoeuvres into his physiotherapy regime with little in the way of symptoms. This has been accompanied by an improvement in his pulmonary functions tests which have shown an FEV1 of 1.89 and FVC of 4.47 (47% and 95% predicted).

Figure 1

Transthoracic echocardiogram demonstrating the patent foramen ovale

Figure 2

Bubble-contrast transthoracic echocardiography with injection of agitated saline. (2a) Opacification of the right atrium (RA) is seen initially; (2b) passage of bubbles into the left atrium (LA) and left ventricle

Discussion

A patent foramen ovale represents the failure of fusion of the valve of the foramen ovale (septum primum) with the atrial septum (septum secundum), ¹ leaving a potential interatrial channel through which venous blood may shunt if the pressure in the right atrium exceeds that in the left. ² Within the general population PFOs are relatively common and are associated with a number of conditions (Box 1). ³

Box 1

Conditions associated with patent foramen ovale

Ischaemic stroke

Pulmonary embolism

COPD

Obstructive sleep apnoea

Gas embolism

Fat embolism

Platyponoea-orthodeoxia syndrome

Migraine

Transient global amnesia

Paradoxical embolism to other organs

Autopsy series have identified a PFO in up to 35% of the general population, with the incidence decreasing with increasing age. ¹ Recently, The Stroke Prevention: Assessment of Risk in a Community (SPARC) study reported the prevalence of PFO in a randomly selected cohort was 25.6% based on transoesophageal echocardiogram (TOE). ⁴ Whether this incidence differs in the CF population is unknown; to date only two studies have reviewed the incidence of PFO in the CF population. Davidson et al. assessed 15 patients with CF, aged 19–44 years, who underwent TOE. ⁵ Patients in this group had advanced disease and were found to have a mean FEV1 of 25.3 ± 7.2% of predicted and an FVC of 45.5 ± 11.9% of predicted. Of the 15 patients, seven individuals (47%) were found to have left-to-right shunting by bubble contrast injection and colour Doppler. Similarly, Espiritu and Kleinhenz described the presence of a PFO in 6 of 11 (55%) patients who underwent either transthoracic echocardiogram (TTE) or TOE at their centre. ⁶ Although the authors do not do not detail the severity of the underlying lung disease, they do describe PFO as the most common echocardiographic finding.

There have been several case reports of CF patients who have developed a neurological deficit from a paradoxical embolism across a PFO. However, these have been almost exclusively in the presence of a totally implantable venous access device (TIVAD) which acts as a site of thrombus formation.^7–9 In the absence of a physical lesion, i.e. embolism, one is left searching for other possible mechanisms by which PFOs might cause neurological symptoms. One possible explanation is that the presence of obstructive lung disease, the increase in intrathoracic pressure causes worsening of the right-to-left shunt across the PFO. During valsalva manoeuvres, most notably coughing, increased intrathoracic pressure is transmitted via valveless veins to the intracranial compartment. The transient increase in intracranial pressure, combined with the delivery of mixed arterial and venous blood, results in impairment of cerebral blood flow as well as cerebral hypoxia. Increased intrathoracic pressure also obstructs venous outflow causing reduced cardiac output and blood pressure resulting in cerebral hypoperfusion. ¹⁰ In the case of severe obstructive lung disease, extreme pressure changes during inspiration can cause physiological tamponade which may interfere with cardiac output and cerebral perfusion. ¹¹

There is currently a great deal of debate relating to when one should attempt PFO closure and whether this offers any significant advantage over either medical or conservative management. ¹² A number of new devices have been developed recently and clinical trials suggest relatively low and acceptable complication rates compared with older devices.^13,14 Debate still exists however with regards to their efficacy in certain clinical conditions such as migraine. ¹⁵ One might argue that CF obstructive airways disease represents a special case for PFO closure; CF patients are at far greater risk of haemoptysis ¹⁶ and life-threatening bleeding ¹⁷ and thus medical therapy, in the form of oral anticoagulants, represents a relatively unappealing option. Furthermore, patients with cystic fibrosis are encouraged to perform forced expiratory manoeuvres on a daily basis which might promote bleeding. A further consideration is the impact that a PFO might have on an individual's ability to undertake daily physiotherapy. Presently, airways clearance techniques form one of the cornerstones of CF management. Although the long-term outcome of daily physiotherapy, such as rates of exacerbations and mortality is not known, ¹⁸ inability to perform these techniques may ultimately result in worsening of their respiratory disease and shortening of life expectancy.

Conclusion

This case demonstrates that in the cystic fibrosis patient, the presence of a patent foramen ovale (and subsequent closure) may have a significant impact on lung function. Additionally PFOs may be associated with neurological manifestations even in the absence of a demonstrable thrombo-embolic lesion. The case highlights the need to further evaluate the incidence of PFOs and their clinical implications in the cystic fibrosis population.