JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 65, NO. 20, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
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,
ventricle
whereas they remained unchanged in the no PFO
pressure.
and
reduced
nocturnal
systolic
blood
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
Letters
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)
100
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]
50
http://dx.doi.org/10.1016/j.jacc.2015.01.062
25
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
75
0
150
Baseline Follow-Up Baseline (After PFO Closure)
Follow-Up
PFO
No PFO
p=0.0093
p=0.36
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-
130
structive sleep apnea: clinical features and effects of closure. Chest 2013;143: 56–63.
120
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
35
REFERENCES
with closure of a patent foramen ovale. J Clin Sleep Med 2007;3:295–6.
140
90
RV-RA Systolic Pressure Gradient (mm Hg)
2258
Baseline Follow-Up Baseline (After PFO Closure) PFO p=0.0034
Follow-Up
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)
Follow-Up
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
VOL. 65, NO. 20, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
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,
ventricle
whereas they remained unchanged in the no PFO
pressure.
and
reduced
nocturnal
systolic
blood
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
Letters
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)
100
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]
50
http://dx.doi.org/10.1016/j.jacc.2015.01.062
25
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
75
0
150
Baseline Follow-Up Baseline (After PFO Closure)
Follow-Up
PFO
No PFO
p=0.0093
p=0.36
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-
130
structive sleep apnea: clinical features and effects of closure. Chest 2013;143: 56–63.
120
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
35
REFERENCES
with closure of a patent foramen ovale. J Clin Sleep Med 2007;3:295–6.
140
90
RV-RA Systolic Pressure Gradient (mm Hg)
2258
Baseline Follow-Up Baseline (After PFO Closure) PFO p=0.0034
Follow-Up
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)
Follow-Up
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
