CPAP treatment promotes the closure of a patent foramen ovale in ...

PATENT FORAMEN OVALE AFTER CPAP TREATMENT

1

CPAP treatment promotes the closure of a patent foramen ovale in subjects with obstructive sleep apnea syndrome – Results from a pilot study Manolo E. Beelke 1 1

Senior Medical Director, M.D., Ph.D Worldwide Clinical Trials (WCT), Medical & Scientific Affairs – Germany

Corresponding Author: Manolo Beelke E-mail Address: [email protected]

Abstract Study Objectives: Patent foramen ovale (PFO) is an independent risk factor for ischemic stroke by means of paradoxical embolization, due to right-to-left shunt (RLSh). The higher prevalence of PFO found in OSAS respect to the general population could be due to the chronic effect of the intrathoracic pressure changes during periods of obstructive sleep apnea. This study aimed to re-evaluate the magnitude of RLSh in subjects with obstructive sleep apnea syndrome (OSAS) and diagnosed PFO after a long period of CPAP treatment. Design and Setting: Assessment of PFO and concomitant OSAS. Application of CPAP treatment with control of compliance. Re-evaluation of RLSh through the assessed PFO at follow-up (after 41  6 months) by means of Transcranial Doppler with contrast medium injected in antecubital vein. Participants: Eighteen OSAS subjects affected by PFO (mean age 56 ± 11 years). Interventions: They underwent Transcranial Doppler, with injection of agitated saline solution mixed with air during normal breathing and Valsalva maneuver. Measurements and Results: CPAP treatment has chronically applied by 15 of 18 subjects (83%). RLSh magnitude did not change in the 3 subjects, who had not applied the CPAP treatment. In 4 of the 15 subjects, who used the CPAP treatment, no RLSh could be recorded (PFO closure). The difference between CPAP-user and CPAP–non-users was significant (p20

treatment, daily use (hours) and weekly

HITS but no curtain pattern’ and ‘> 20

use (days/week), the CPAP treatment

HITS with curtain pattern’ (Beelke et al.,

pressure (mbar), age, the condition of

2003; Jauss & Zanette, 2000; Angeli et al.,

atrial fibrillation, the number of HITS at

2001).

baseline recording.

ORIGINAL

has

multiple

been

Statistical analysis

of RLSh

backward

7 All computations were performed using

one subject referred episodes of migraine

the SAS package (software version 6, SAS

without aura. As far as increased risk for

Inc., 1990).

strokes regards due to comorbidity of atrial fibrillation, only one subject of the study Results

sample suffered this condition.

Though for years, many experts have postulated a cause-and-effect relationship between migraine headaches and PFO (Schwedt, Demaerschalk, & Dodick, 2008; Kurth, Tzourio, & Bousser, 2008), only

Among the 15 subjects who used CPAP treatment, compliance was good with a mean daily use of 6.6 ± 1.5 hours and a meanly weekly use of 6 ± 1 days a week (see table 1).

Table 1: Features of the OSAS Sample Subject

Age (yrs.)

Sex

MwA

AF CPAP use

CPAP treatment months daily days/ hours week

CPAP press. (mbar) 1 55 F n N Y 46 7 7 12 2 53 F n N Y 42 9 7 14 3 64 M n N Y 46 6 5 12 4 49 M n N Y 45 5 2 12 5 42 M n N Y 45 7 7 13 6 63 M n N Y 45 5 7 14 7 43 M n N Y 44 7 7 7 8 33 M n N Y 32 7 7 10 9 64 M n N Y 44 9 7 9 10 58 M n N Y 46 6 6 11 11 44 M n N Y 44 4 6 8 12 70 M n N N 0 0 0 6 13 62 M n N Y 39 7 7 12 14 55 M n Y Y 36 5 7 15 15 56 F y N N 0 0 0 12 16 56 M n N Y 31 8 7 11 17 61 F n N N 0 0 0 10 18 78 M n N Y 30 7 5 10 Mean (SD) 56 (11) *41 (6)* *7 (2) *6 (1) *11 (2) MwA, migraine without aura; AF, atrial fibrillation, F, female; M, male; y, yes; n, no; SD, Standard Deviation Note: Highlighted in grey are those subjects, who have not used CPAP during the follow-up period. *Mean value and Standard deviation calculated only for subjects, who used the CPAP

Despite the small sample size, analysis by

for the CPAP users (p 20 HITS with curtain pattern’.

No significant differences could be shown

seen in 11 of 15 subjects (73%). An

for the number of HITS recorded during

increase

physiologic respiration (see table 2). In

maneuver at follow-up has been observed

particular, during Valsalva maneuver in 4

only in 1 subjects, although the ESS score

of 15 subjects (27%) no HITS could be

decreased from 21 at baseline to 0 at

recorded at follow-up (100% reduction). A

follow-up (see table 2).

reduction

Valsalva

No statistically significant differences

maneuver at follow-up with respect to the

were present for the BMI neither between

in

HITS

during

baseline recording of at least 50% has been

ORIGINAL

of

HITS

during

Valsalva

10 groups and nor between time (follow-up

of the daily hours of use. The lack of an

respect to baseline).

impact of the daily use of the CPAP device

No significant differences has been found

might however not seen in this sample due

for the latency to the microembolic signal

to the high daily use (7 ± 2 hours daily).

and for the BMI. When multiple regression

OSAS subjects with PFO of little size can

analysis was applied, the weekly CPAP

reveal at follow-up an absolute complete

use (days/week) and the condition of atrial

closure of the PFO (see, table 2). PFO’s of

fibrillation were recognized as these

middle and large size, however show only

factors,

the

a partial closure, shifting generally in the

amount of HITS at follow-up. In this

next lower class (see table 3; see figure 4).

model the number of days of weekly

In subjects with PFO of large size and

CPAP

the

shunting already at rest, the decrease of the

was

magnitude of RLSh at follow-up is not

positively correlated to the number of

characterized by a shift in the next lower

HITS recorded at follow-up.

class (see figure 4 and figure 5).

Discussion

previous studies, the diameter of a PFO

In this study it has been shown for the first

has been shown to be an independent risk

time that the daily application of CPAP

factor for ischemic events, especially

treatment reduce the magnitude of RLSh

recurrent

in those OSAS subjects, who present

Johnson, 1999; Serena et al., 1998). The

concomitantly a PFO, where the non-use

occurrence of PFO has been associated to

do not change the PFO size. In the study

genetic factors, especially to mutations of

sample, the treatment effect of the CPAP

the homeobox gene NKX2-5, but the

device use appears to be related more to

importance of these factors in sporadic

which

use

condition

mainly

was of

influence

negatively

atrial

and

fibrillation

the weekly CPAP use (days/week) instead

ORIGINAL

strokes (Cujec,

Mainra,

In

&

11 PFO is still open to debate (Elliott et al.,

2003; Schott et al., 1998).

Table 3: Group shifts of RLSh grading in terms of absolute and relative numbers for the 15 CPAP users Baseline

no RLSh Small Middle large - curtain large + curtain

at-rest Shunting Absolute Percentage 11 69% 2 13% 1 6% 1 6% 0 0%


at-rest Shunting Absolute Percentage 12 75% 3 19% 0 0% 0 0% 0 0%

provocative Shunting Absolute Percentage 0 0% 8 50% 4 25% 2 13% 1 6%

Follow-up provocative Shunting Absolute Percentage 4 25% 9 56% 2 13% 0 0% 0 0%

Differences


at-rest Shunting Absolute Percentage 1 6% 1 6% -1 -6% -1 -6% 0 0%

provocative Shunting Absolute Percentage 4 25% 1 6% -2 -13% -2 -13% -1 -6%

Figure 4: RLSh grading in CPAP users before and after CPAP treatment

Frequency

Provocative shunting PFO (RLSh with Valsalva) 20

baseline

15

follow-up

10 5 0

no RLSh

small

middle

RLSh grading ~

ORIGINAL

large - c

large + c

12

Frequency

At-rest shunting PFO (RLSh with normal respiration)

14 12 10 8 6 4 2 0

baseline follow-up

no RLSh

small

middle

large - c

large + c

RLSh grading Figure 4. RLSh grading was reduced at follow-up for provocative shunting PFO in subjects, who used the CPAP device.

Figure 5: Individual RLSh in CPAP users before and after CPAP treatment

Figure 5. The graphic representation of individual RLSh shift at follow-up emphasizes how strong the reduction of the RLSh was in some individuals.

ORIGINAL

13 In a previous study (Beelke et al., 2002), it

The well reported high morbidity and

has been shown that nocturnal sleep apnea

mortality in OSAS (Bassetti et al., 1997;

could act like the Valsalva maneuver in

Pressman et al., 1995; Dyken, Somers,

opening of a provocative shunting PFO.

Yamada, Ren, & Zimmerman, 1996;

This study suggests therefore that the

Wessendorf, Teschler, Wang, Konietzko,

chronic

apnea-dependent

& Thilmann, 2000), related particularly to

mechanical factors may influences the size

stroke, can be explained by the sequential

of a PFO. In fact, these mechanical factors

pathophysiological

start to act already at the beginning of an

occurring during periods of nocturnal

obstructive apnea, where an inspiratory

obstructive apneas, can compromise the

effort against a closed upper airway is

brain circulation (Szücs et al., 2002;

present, inducing a decrease in end-

Trzebski & Śmietanowski, 2001). Chronic

inspiratory pleural pressure. This event is

CPAP treatment has commonly seen to

followed by swings of increasing end

reduce the risk for stroke (Diomedi,

decreasing effects on pleural pressure,

Placidi, Cupini, Bernardi, & Silvestrini,

influencing directly the interatrial pressure

1998; Akashiba et al., 1999). Data from

balance and the increase of inspiratory

this study suggest, indirectly, that this

venous return. The consequent right-sided

stroke-protective effect may not only be

pressure increase will then be at the origin

linked to hematologic and arteriosus

of the RLSh through a PFO. The chronic

pressure features, but also to the ability to

effect of such a mechanism could also

reduce the size of a PFO, or absolutely

explain the higher prevalence of PFO in

close it. However, to obtain this effect, a

subjects with OSAS respect to the control

high compliance to the CPAP treatment

group (Shanoudy et al., 1998; Beelke et

seems to be a prerequisite.

effect

al., 2003).

ORIGINAL

of

events,

which,

14 This study shows furthermore, that in

of RLSh decrease due to the CPAP

subjects with a PFO of big size before

treatment,

treatment and in those subjects with an

approaches as surgical closure of PFO

RLSh

normal

(Thaler et al., 2017), or life-long treatment

respiration, the decrease of the RLSh at

with anticoagulants or antiplatelet agents

follow-up

partially.

should be considered at least, till a follow-

Considering, that at the moment of

up TcD examination do not show a

diagnosis of PFO in a subject with OSAS

spontaneous PFO closure or a PFO of little

it is impossible to preview the magnitude

size.

already

at

will

rest

be

with

only

additional

therapeutic

Angeli, S., Del Sette, M., Beelke, M.,

References

Anzola, G. P., & Zanette, E. (2001). Akashiba, T., Minemura, H., Yamamoto, H., Kosaka, N., Saito, O., & Horie, T. (1999).

Nasal

Airway

Continuous

Pressure

Changes

Positive Blood

Pressure “Non-dippers” to “Dippers” in Patients With Obstructive Sleep Apnea. Sleep, 22(7), 849–853. Retrieved from http://dx.doi.org/10.1093/sleep/22.7.84 9

Transcranial Doppler in the diagnosis of

cardiac

ovale.

Neurological Sciences, 22(5), 353–356. doi: 10.1007/s100720100064

Bassetti, C., Aldrich, M. S., & Quint, D. (1997). Sleep-Disordered Breathing in Patients

1765 LP Aortic Arch Atheroma, Patent Foramen and

the

Cerebrovascular

Risk

of

With

Acute

Supra-

and

Diseases,

20(suppl

http://www.karger.com/DOI/10.1159/0 00089358

– 1772. Retrieved from

http://stroke.ahajournals.org/content/28/ 9/1765.abstract

Stroke.

2(Suppl. 2), 68–74. Retrieved from

Beelke, M., Angeli, S., Del Sette, M., De Carli, F., Canovaro, P., Nobili, L., & Ferrillo, F. (2002). Obstructive sleep apnea can be provocative for right-to-left

ORIGINAL

foramen

Infratentorial Strokes. Stroke, 28(9),

Amarenco, P. (2005). Cryptogenic Stroke,

Ovale,

patent

shunting

through

a

15 patent foramen ovale. Sleep, 25(8), 856–862.

Retrieved

from

Chant, H., & McCollum, C. (2001). Stroke in Young Adults: The Role of

http://europepmc.org/abstract/MED/

Paradoxical Embolism. Thrombosis

12489891

and Haemostasis, 85(1), 22–29. Retrieved

Beelke, M., Angeli, S., Del Sette, M., De Carli, F., Canovaro, P., Nobili,

from

http://www.schattauer.de/t3page/121 4.html?manuscript=2637&L=1

L., & Ferrillo, F. (2002). Obstructive sleep apnea can be provocative for right-to-left

shunting

through

Clarenbach, P., & Wessendorf, T.

a

(2001). Sleep and stroke. Revue

patent foramen ovale. Sleep, 25(8),

neurologique, 157(11 Pt 2), S46-52.

856–862.

Retrieved

Retrieved

from

from


http://europepmc.org/abstract/med/1

12489891

1924038

Beelke, M., Angeli, S., Del Sette, M., Gandolfo,

C.,

Cabano,

M.

E.,

Cujec, B., Mainra, R., & Johnson, D. H. (1999).

Prevention

of

recurrent

Canovaro, P., … Ferrillo, F. (2003).

cerebral ischemic events in patients

Prevalence of patent foramen ovale

with patent foramen ovale and

in subjects with obstructive sleep

cryptogenic

apnea:

Doppler

ischemic attacks. The Canadian

ultrasound study. Sleep Medicine,

Journal of Cardiology, 15(1), 57–64.

4(3), 219–223. doi:10.1016/S1389-

Retrieved

9457(02)00256-3


a

transcranial

strokes

or

transient

from

10024860 Biswas, M., Prakash, P. K., Cossburn, M., Myers, K., & Hanna, F. (2003). Life-threatening complications

thrombotic of

relative

Diomedi, M., Placidi, F., Cupini, L. M., Bernardi, G., & Silvestrini, M. (1998).

Cerebral

hemodynamic

polycythaemia. Journal of Internal

changes in sleep apnea syndrome

Medicine,

and effect of continuous positive

253(4),

481–483.

doi:10.1046/j.1365-

airway

2796.2003.01126.x

Neurology , 51 (4 ), 1051–1056. Retrieved

ORIGINAL

pressure

treatment.

from

16 http://www.neurology.org/content/51

Patients:

A

Contrast

/4/1051.abstract

Transesophageal Echocardiography Study. Chest, 107(6), 1504–1509.

Dyken, M. E., Somers, V. K., Yamada,

doi:10.1378/chest.107.6.1504

T., Ren, Z.-Y., & Zimmerman, M. B. (1996).

Investigating

the

Geiser, T., Buck, F., Meyer, B. J.,

Relationship Between Stroke and

Bassetti, C., Haeberli, A., & Gugger,

Obstructive Sleep Apnea. Stroke,

M.

27(3), 401 LP – 407. Retrieved from

Activation Is Increased during Sleep

http://stroke.ahajournals.org/content/

in Patients with Obstructive Sleep

27/3/401.abstract

Apnea

(2002).

In

vivo

Syndrome.

Platelet

Respiration,

69(3), 229–234. Retrieved from Eisensehr, I., & Noachtar, S. (2001). Haematological

aspects

of

obstructive

apnoea.

Sleep

sleep

Medicine Reviews, 5(3), 207–221. doi:10.1053/smrv.2001.0158

http://www.karger.com/DOI/10.1159 /000063625

Hagen, P. T., Scholz, D. G., & Edwards, W. D. (1984). Incidence and Size of Patent Foramen Ovale

Elliott, D. A., Kirk, E. P., Yeoh, T.,

During the First 10 Decades of Life:

Chandar, S., McKenzie, F., Taylor,

An Autopsy Study of 965 Normal

P., … Harvey, R. P. (2003). Cardiac

Hearts. Mayo Clinic Proceedings,

homeobox gene NKX2-

59(1), 17–20. doi:10.1016/S0025-

5mutations

6196(12)60336-X

and

congenital heart disease. Journal of the American College of Cardiology,

Itoh, T., Matsumoto, M., Handa, N.,

41(11), 2072 LP – 2076. Retrieved

Maeda,

from

Tsukamoto, Y., … Kamada, T.

http://www.onlinejacc.org/content/4

(1994). Paradoxical embolism as a

1/11/2072.abstract

cause of ischemic stroke of uncertain

H.,

Hougaku,

H.,

etiology. A transcranial Doppler Fisher, D. C., Fisher, E. A., Budd, J. H.,

sonographic study. Stroke, 25(4), – 775. Retrieved from

Rosen, S. E., & Goldman, M. E.

771 LP

(1995). The Incidence of Patent


Foramen Ovale in 1,000 Consecutive

25/4/771.abstract

ORIGINAL

17 http://circ.ahajournals.org/content/11 Jauss, M., & Zanette, E. (2000).

8/14/1405.abstract

Detection of Right-to-Left Shunt with Ultrasound Contrast Agent and

Lechat, P., Mas, J. L., Lascault, G.,

Transcranial Doppler Sonography.

Loron, P. H., Theard, M., Klimczac,

Cerebrovascular Diseases, 10(6),

M., … Grosgogeat, Y. (1988).

490–496.

Prevalence of Patent Foramen Ovale

Retrieved

from

http://www.karger.com/DOI/10.1159

in

Patients

/000016119

England

with

Journal

318(18), Kiely, J. L., & McNicholas, W. T. (2000). Cardiovascular risk factors

Stroke. of

New

Medicine, 1148–1152.

doi:10.1056/NEJM19880505318180 2

in patients with obstructive sleep apnoea

syndrome.

European

Lynch, J. J., Schuchard, G. H., Gross,

Respiratory Journal, 16(1), 128 LP

C. M., & Wann, L. S. (1984).

–

Prevalence of

133.

Retrieved

from

right-to-left

atrial

http://erj.ersjournals.com/content/16/

shunting in a healthy population:

1/128.abstract

detection by Valsalva maneuver contrast

Klötzsch, C., Janßen, G., & Berlit, P. (1994).

Transesophageal

echocardiography.

The

American Journal of Cardiology, 53(10),

1478–1480.

echocardiography and contrast‐TCD

doi:10.1016/S0002-9149(84)91617-

in the detection of a patent foramen

5

ovale: Experiences with 111 patients . Neurology , 44 (9 ), 1603.

M, D. T., RL, S., Gopal, A., JP, M., &

from

Homma, S. (1992). PAtent foramen

http://www.neurology.org/content/44

ovale as a risk factor for cryptogenic

/9/1603.abstract

stroke. Annals of Internal Medicine,

Retrieved

117(6), 461–465. Retrieved from Kurth, T., Tzourio, C., & Bousser, M.G. (2008). Migraine. Circulation,

http://dx.doi.org/10.7326/00034819-117-6-461

118(14), 1405 LP – 1407. Retrieved from

Maraj, R., Ahmed, O., Fraifeld, M., Jacobs, L. E., Yazdanfar, S., &

ORIGINAL

18 Kotler, M. N. (1999). Hypoxia due

https://www.researchgate.net/profile/

to patent foramen ovale in the

Lino_Nobili2/publication/12603614

absence of pulmonary hypertension.

_Morning_increase_of_whole_blood

Texas Heart Institute Journal, 26(4),

_viscosity_in_obstructive_sleep_apn

306–308.

ea_syndrome/links/55ba3fec08aed62

Retrieved

from

http://www.ncbi.nlm.nih.gov/pmc/art

1de0aca93.pdf

icles/PMC325672/ Parra, O., Arboix, A., Bechich, S., Movsowitz,

C.,

Podolsky,

A.,

García-Eroles, L., Montserrat, J. M.,

Meyerowitz, C. B., Jacobs, L. E., &

López, J. A., … Sopeña, J. J. (2000).

Kotler,

Time

M.

N.

(1992).

L.

Patent

Course

of

Sleep-related

Foramen Ovale: A Nonfunctional

Breathing Disorders in First-Ever

Embryological

a

Stroke or Transient Ischemic Attack.

Significant

American Journal of Respiratory

Pathology? Journal of the American

and Critical Care Medicine, 161(2),

Society of Echocardiography, 5(3),

375–380.

259–270.

doi:10.1164/ajrccm.161.2.9903139

Potential

Remnant

Cause

of

or

doi:10.1016/S0894-

7317(14)80346-5 Partinen, M., & Guilleminault, C. Neau, J.-P., Paquereau, J., Meurice, J.-

(1990). Daytime Sleepiness and

C., Chavagnat, J.-J., & Gil, R.

Vascular Morbidity at Seven-Year

(2002). Stroke and sleep apnoea:

Follow-up

cause

Apnea Patients. Chest, 97(1), 27–32.

or

consequence?

Sleep

Medicine Reviews, 6(6), 457–469.

in

Obstructive

Sleep

doi:10.1378/chest.97.1.27

doi:10.1053/smrv.2002.0207 Placidi, F., Diomedi, M., Cupini, L. M., Nobili, L., Schiavi, G., Bozano, E., De

Bernardi, G., & Silvestrini, M.

Carli, F., Ferrillo, F., & Nobili, F.

(1998).

(2000). Morning increase of whole

cerebrovascular reactivity in patients

blood viscosity in obstructive sleep

with

apnea

syndrome. Clinical

syndrome.

Journal

and

Research,

7(4),

hemorheology microcirculation, 22(1), Retrieved ORIGINAL

Impairment

obstructive

21-27.

doi:10.1046/j.1365-

from

2869.1998.00120.x

of

daytime

sleep

apnoea

of

Sleep

288–292.

19 Pressman, M. R., Schetman, W. R.,

Meinertz, T. (1996). Diagnosis of

Figueroa, W. G., Van Uitert, B.,

patent

Caplan, H. J., & Peterson, D. D.

transesophageal

(1995). Transient Ischemic Attacks

and

and Minor Stroke During Sleep.

findings. The American Journal of

Stroke, 26(12), 2361 LP – 2365.

Cardiology,

Retrieved

doi:10.1016/S0002-9149(96)00163-

from


foramen

ovale

by

echocardiography

correlation

with

77(14),

autopsy

1202–1209.

4

26/12/2361.abstract Schott, J.-J., Benson, D. W., Basson, C. Ranoux, D., Cohen, A., Cabanes, L.,

T., Pease, W., Silberbach, G. M.,

Amarenco, P., Bousser, M. G., &

Moak, J. P., … Seidman, J. G.

Mas, J. L. (1993). Patent foramen

(1998). Congenital Heart Disease

ovale: is stroke due to paradoxical

Caused

embolism? Stroke, 24(1), 31 LP –

Transcription

34.

NKX2-5

Retrieved

from

by

Mutations

in

the

Factor


Science, 281(5373), 108 LP – 111.

24/1/31.abstract

Retrieved

from

http://science.sciencemag.org/conten Sanner, B. M., Konermann, M., Tepel,

t/281/5373/108.abstract

M., Groetz, J., Mummenhoff, C., & Zidek, W. (2000). Platelet function

Schuchlenz, H. W., Weihs, W., Horner,

in patients with obstructive sleep

S., & Quehenberger, F. (2000). The

apnoea

European

association between the diameter of

Respiratory Journal, 16(4), 648 LP

a patent foramen ovale and the risk

–

from

of embolic cerebrovascular events.

http://erj.ersjournals.com/content/16/

The American Journal of Medicine,

4/648.abstract

109(6),

syndrome.

652.

Retrieved

456–462.

doi:10.1016/S0002-9343(00)00530SAS Institute Inc.(1990). User’s guide:

1

statistics. Version 6. Cary, NC: SAS. Schwedt, T. J., Demaerschalk, B. M., & Schneider, B., Zienkiewicz, T., Jansen, V., Hofmann, T., Noltenius, H., & ORIGINAL

Dodick,

D.

W.

(2008).

Patent

foramen ovale and migraine: a

20 quantitative

systematic

Cephalalgia,

28(5),

review. 531–540.

19(6),

1192–1196.

doi:10.1016/0735-1097(92)90323-F

doi:10.1111/j.14682982.2008.01554.x

Strunk, B. L., Cheitlin, M. D., Stulbarg, M. S., & Schiller, N. B. (1987).

Serena, J., Segura, T., Perez-Ayuso, M.

Right-to-left

interatrial

shunting

J., Bassaganyas, J., Molins, A., &

through a patent foramen ovale

Dávalos, A. (1998). The Need to

despite

Quantify Right-to-Left Shunt in

pressures. The American Journal of

Acute

Cardiology,

Ischemic

Stroke.

Stroke,

29(7), 1322 LP – 1328. Retrieved

normal

intracardiac

60(4),

413–415.

doi:10.1016/0002-9149(87)90271-2

from http://stroke.ahajournals.org/content/ 29/7/1322.abstract

Szücs, A., Vitrai, J., Janszky, J., Migléczi, G., Bódizs, R., Halász, P., & Nagy, Z. (2002). Pathological

Shanoudy, H., Soliman, A., Raggi, P.,

Sleep Apnoea Frequency Remains

Liu, J. W., Russell, D. C., &

Permanent in Ischaemic Stroke and

Jarmukli, N. F. (1998). Prevalence of

It Is Transient in Haemorrhagic

Patent

Foramen

Contribution

to

Patients

with

Apnea.

Chest,

Ovale

and

Its

Stroke. European Neurology, 47(1),

Hypoxemia

in

15–19.

Obstructive

Sleep

113(1),

91–96.

Retrieved

from

http://www.karger.com/DOI/10.1159 /000047941

doi:10.1378/chest.113.1.91 Thaler, D., Carroll, J., Saver, J., Siostrzonek, P., Lang, W., Zangeneh,

Smalling,

R.,

MacDonald,

L.,

M., Gössinger, H., Stümpflen, A.,

Larkin, B., … Tirschwell, D. (2017).

Rosenmayr, G., … Mösslacher, H.

Abstract 71: PFO Closure Reduces

(1992). Significance of left-sided

Long Term Recurrence of Ischemic

heart disease for the detection of

Stroke: Final Primary and Secondary

patent

Population

foramen

transesophageal

ovale

by

contrast

Results

From

RESPECT Multicenter Trial. Stroke,

echocardiography. Journal of the

48(Suppl 1), A71 LP

American College of Cardiology,

Retrieved

ORIGINAL

the

– A71. from

21 http://stroke.ahajournals.org/content/

(1988). Patent foramen ovale in

48/Suppl_1/A71.abstract

young stroke patients. The Lancet, 332(8601),

Trzebski, A., & Śmietanowski, M. (2001).

Non-linear

dynamics

of

11–12.

doi:10.1016/S0140-6736(88)929443

cardiovascular system in humans exposed

to

repetitive

apneas

Wessendorf, T. E., Teschler, H., Wang,

modeling obstructive sleep apnea:

Y.-M., Konietzko, N., & Thilmann,

aggregated time series data analysis.

A.

Autonomic Neuroscience, 90(1–2),

breathing among patients with first-

106–115.

ever stroke. Journal of Neurology,

doi:10.1016/S1566-

0702(01)00275-2

F.

(2000).

Sleep-disordered

247(1),

41–47.

doi:10.1007/PL00007787 Voogel, A. J., van Steenwijk, R. P., Karemaker, J. M., & van Montfrans,

Yeung, M., Khan, K. A., & Shuaib, A.

G. A. (1999). Effects of treatment of

(1996).

obstructive sleep apnea on circadian

ultrasonography in the detection of

hemodynamics.

venous to arterial shunting in acute

Journal

of

the

Autonomic Nervous System, 77(2–3),

stroke

177–183.

attacks.

doi:10.1016/S0165-

1838(99)00039-9

Transcranial

and

transient

Journal

of

Neurosurgery

Doppler

ischaemic Neurology, &

Psychiatry, 61(5), 445 LP – 449. Webster, M. W. I., Smith, H. J., Sharpe,

Retrieved

from

D. N., Chancellor, A. M., Swift, D.

http://jnnp.bmj.com/content/61/5/44

L., Bass, N. M., & Glasgow, G. L.

5.abstract

Disclosure

these institutions anymore.

This study has been performed at the

Acknowledgment

Center

of

Sleep

Medicine,

DISMR,

University of Genoa, Italy and the Stroke Unit, Department of Neurosciences and Neurorehabilitation, University of Genoa,

I thank Silvia Angeli for support during transcranial

Doppler

assessments

Massimo Del Sette for creative and educational

Italy.

exchange.

The author is currently not working at How to cite this Article: Beelke, M. (2017). CPAP treatment promotes the closure of a patent foramen ovale in subjects with obstructive sleepORIGINAL apnea syndrome –Results from a pilot study.. International Journal of Psychology and Neuroscience, 3(1), 1-21. Received: 15/03/2017;

Revised: 10/04/2017;

Accepted: 14/04/2017;

and

Published online: 30/04/2017;

ISBN 2183-5829