VOL. 65, NO. 20, 2015


ISSN 0735-1097/$36.00


Letters Effect of Patent Foramen Ovale Closure on Obstructive Sleep Apnea

This first clinical investigation on the effect of PFO closure on OSA found a reduction of approximately 8 AHI events per hour in response to PFO closure. This reduction was accompanied by a mitigated ODI, by a nocturnal systemic blood pressure reduction of 5 mm Hg, and by lowered pulmonary pressure values

Patent foramen ovale (PFO) is a prevalent embryo-

with enhanced left ventricular diastolic function.

logic remnant with insufficient post-natal adhesion of

A causal relation between PFO and OSA would be

the cardiac atrial septum primum and secundum.

evident if a positive effect on OSA of PFO closure

Among many other conditions, it has been associated

could be systematically documented. So far, the effi-

with obstructive sleep apnea (OSA) syndrome. The

cacy of PFO closure on OSA parameters has only been

mechanism operative in these conditions is tempo-

implied in case reports (1–3).

rary right-to-left atrial shunting across the “open

Pathophysiologically, PFO appears to have an

door” of the septum primum, which leads to short

exacerbating effect on phasic breathing in OSA. The

bouts of arterial de-oxygenation. The effect of PFO

crucial element in this context is short events of atrial

closure on OSA has not been investigated to date. We

right-to-left shunts with ensuing episodes of hypox-

tested whether PFO closure in OSA patients led to a

emia, which aggravate the already disturbed central

lowering of the apnea–hypopnea index (AHI) and to

breathing regulation in OSA. The initiating incident in

improved cardiovascular function.

the cascade of phasic breathing in OSA is the first ap-

This prospective open-label study included 40

nea in the context of muscular relaxation during rapid

consecutive patients with newly diagnosed OSA.

eye movement sleep. Rising arterial pressure of carbon

Fourteen of them had PFOs diagnosed by trans-

dioxide (PCO 2) in the context of this apnea induces

esophageal contrast echocardiography; these patients

breathing efforts against the closed glottis, which

underwent initial device closure. Twenty-six patients

briefly elevates right atrial pressure above left atrial

did not have PFOs. Conventional treatment for OSA

pressure and leads to shunting of de-oxygenated

was postponed for 3 months in both groups, and pol-

blood to the systemic side in cases of a PFO. Hypox-

ysomnographic and cardiovascular examinations were

emia impairs endothelial function in the pulmonary

performed at baseline and at the end of the follow-up

and in the systemic circulation, and it acts as a central

period. The following endpoints were compared

respiratory stimulant, which influences the PCO 2-

intra- and interindividually: AHI (primary endpoint);

steered respiratory regulation differently from other

oxygen de-saturation index (ODI) (drops in oxygen

stimulants (4). Hypoxemia lowers the eupneic PCO 2

saturation >3% points per hour); systemic arterial

level in the context of hyperventilation without

blood pressure; and Doppler echocardiographic pa-

concomitant reduction in the apneic PCO2 threshold,

rameters. During follow-up, AHI decreased from 38.6 

thus destabilizing the system and rendering it more

16.0 to 30.4  16.1 events per hour in the PFO closure

prone to ensuing apnea phases (4). In this scenario, the

group (p ¼ 0.0034), and it changed from 33.9  29.8 to

elevated sympathetic tone with increased systemic

38.6  26.2 events per hour in the no PFO group (p ¼

blood pressure is related to the events of arousal at the

0.29) (Figure 1). AHI change (follow-up minus baseline

end of the apnea phases. Our study results support this

value) differed significantly between the groups: –7.9

concept by showing a normalization of the estimated

 10.4 in the PFO closure group and þ4.7  13.1 in the no

pulmonary pressure in response to PFO closure,

PFO group (p ¼ 0.0009). The following parameters

together with augmented diastolic function of the left

improved significantly in the PFO closure group,


whereas they remained unchanged in the no PFO







group: ODI; a decrease in nocturnal systolic blood

The main study limitations are the nonrandomized

pressure (Figure 1) and daytime blood pressure; right

design, which was appropriate in the context of this

ventricular-to-right atrial systolic pressure gradient

first-in-man study, the low number of patients

(Figure 1); and left ventricular diastolic function.

included, and the lack of female patients.

JACC VOL. 65, NO. 20, 2015


MAY 26, 2015:2257–64

F I G U R E 1 Individual Changes in Apnea–Hypopnea Index and

Systolic Blood Pressure Obtained at Baseline and at the 3-Month Follow-Up Examination in Patients With and Without PFO

Apnea-Hypopnea Index, AHI (Events/h)


No PFO p=0.29

Roman Brenner, MD Urs Scherrer, MD Bernhard Meier, MD Matthias Gugger, MD Yves Allemann, MD *Christian Seiler, MD *University Hospital CH-3010 Bern Switzerland E-mail: [email protected]



Please note: Dr. Meier has received research grants to the Department of Cardiology and speaker fees from St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Rimoldi and Ott contributed equally to this study.

160 Nighttime Systolic Blood Pressure (mm Hg)

PFO p=0.0034




Baseline Follow-Up Baseline (After PFO Closure)






1. Agnoletti G, Iserin L, Lafont A, Sidi D, Desnos M. Obstructive sleep apnoea and patent foramen ovale: successful treatment of symptoms by percutaneous foramen ovale closure. J Interv Cardiol 2005;18:393–5. 2. Silver B, Greenbaum A, McCarthy S. Improvement in sleep apnea associated

3. Shaikh ZF, Jaye J, Ward N, et al. Patent foramen ovale in severe ob-


structive sleep apnea: clinical features and effects of closure. Chest 2013;143: 56–63.


4. Xie A, Skatrud JB, Dempsey JA. Effect of hypoxia on the hypopnoeic and apnoeic threshold for CO2 in sleeping humans. J Physiol 2001;535: 269–78.

110 100



with closure of a patent foramen ovale. J Clin Sleep Med 2007;3:295–6.



RV-RA Systolic Pressure Gradient (mm Hg)


Baseline Follow-Up Baseline (After PFO Closure) PFO p=0.0034


No PFO p=0.94

30 25 20 15

Emergency Department Management of Atrial Fibrillation in the United States Versus Ontario, Canada Survey data suggest that there is considerable inter-

Baseline Follow-Up Baseline (After PFO Closure)


Individual changes in the apnea–hypopnea index (upper panel)

national variation in the emergency department (ED) management of patients with atrial fibrillation (AF) (1–3). Hospitalization is common in the United States (2), where nearly 70% of ED visits for AF end in

obtained at baseline and at the 3-month follow-up examination

hospitalization (2,3); this has remained constant

in patients with patent foramen ovale (PFO) and in patients

since 2000 (2,3). By comparison, in Canada’s most

without PFO. Changes in nocturnal systolic blood pressure and in

populous province

Effect of patent foramen ovale closure on obstructive sleep apnea.

Effect of patent foramen ovale closure on obstructive sleep apnea. - PDF Download Free
200KB Sizes 2 Downloads 11 Views