Main topic
Herz 2021 · 46:445–451
https://doi.org/10.1007/s00059-021-05061-y
Accepted: 21 July 2021
Published online: 31 August 2021
© Springer Medizin Verlag GmbH, ein Teil von
Springer Nature 2021
Introduction
While closure of persistent foramen ovale
(PFO) has been a controversial issue in
the secondary prevention of recurrent
ischemic “cryptogenic” stroke, recent
evidence from several large random-
ized prospective multicenter studies has
demonstrated superiority of PFO closure
compared to medical therapy [1–3]. The
term “cryptogenic” stroke in the pres-
ence of PFO has also changed into PFO-
associated stroke [4]. Of note, PFO has
also been associated with several other
conditions, e.g., decompression sick-
ness, migraine, arterial deoxygenation
syndromes [5].
In this review, we summarize the cur-
rent knowledge of PFO anatomy, imag-
ing and required clinical information for
informed decision making and interven-
tional aspects of PFO closure.
Embryology, anatomy, and
prevalence of PFO
The development of the heart involves
complex adaptations during the gesta-
tional period. Around the 4th gestational
week, the primordial single atrium starts
to divide into a left and right atrium
through development of the interatrial
septum [6]. Around the 7th week of ges-
tation, the septum secundum forms with
an infolding that develops into the fora-
men ovale. The septum primum func-
tions primarily as a valve, allowing blood
flow only from the right to the left side
of the developing heart [7]. Before birth,
the PFO is required for physiologic blood
Aurel Maloku1 · Ali Hamadanchi1 · Marcus Franz1 · Gudrun Dannberg1 ·
Albrecht Günther2 · Carsten Klingner2 · P. Christian Schulze1 · Sven Möbius-
Winkler1
1
Department of Internal Medicine I, Cardiology, Angiology, Intensive Medical Care, University Hospital
Jena, Jena, Germany
2
Hans-Berger-Department of Neurology, University Hospital Jena, Jena, Germany
Patent foramen ovale—When to
close and how?
circulation of the fetus in the absence of
functional blood flow through the lungs;
it usually closes within a few years after
birth. Notably, the first to describe a PFO
was Leonardo da Vinci in 1513 [8].
In an autopsy study of 965 normal
hearts, a PFO was found in 27.3% of the
cases [9]. A transesophageal echocar-
diography study in 581 subjects found
a prevalence of 25.6% in normal healthy
subjects [10]. The prevalence of PFO
is higher in patients with bicuspid aor-
tic disease (up to 10-fold increase) [11].
There is no significant difference in re-
gard to sex [9] or race/ethnicities [12].
In an autopsy study, PFO size in adults
varied from 1–19 mm (average 4.9 mm)
[9] and it was found that the diameter
increases with age [13]. Several studies
have shown that the risk of paradoxi-
cal embolism correlates to the size of the
PFO but also with other factors like atrial
septal aneurysm or spontaneous left-to-
right shunt [14, 15].
Role of echocardiography in the
evaluation of patent foramen
ovale
Effective management of PFO-associated
stroke relies primarily and perhaps ex-
clusively on an accurate and comprehen-
sive imaging diagnosis. In this context,
echocardiography plays a critical role.
Echocardiography is utilized for diagno-
sis and risk stratification as well as proce-
dural planning for PFO closure. Further,
it provides intraprocedural guidance and
postprocedural follow-up during inter-
ventional closure [16–19].
While a transesophageal echocardio-
gram (TEE) is usually considered the ref-
erence standard for shunt identification,
a transthoracic echocardiogram (TTE)
with an enhancing agent has recently
gained more attention as the initial test
because of high sensitivity and less inva-
siveness [16]. Current guidelines recom-
mend screening of PFO with bubble test-
transcranial Doppler or TEE in patients
with embolic stroke of undetermined eti-
ology (Grade of Evidence A, according to
ESO-Karolinska Stroke Update Confer-
ence, Stockholm 11–13 November 2018)
[20].
Forpurposes ofconsistencyinnomen-
clature, the American Society of Echocar-
diography [21] has developed a partic-
ular terminology (. Table 1; [21]). It is
important to emphasize that an atrial
septal aneurysm, a redundant saccular
protrusion of the septum into an atrium
is uncommon in the general population
(ca. 1–4% of subjects) [22] but when
present is associated with a PFO in more
than 60% of cases [23].
A summary of the practical aspects
and main topics such as the compari-
son between TTE vs. TEE, pitfalls of
echocardiographic diagnosis with perti-
nent solution and morphological classifi-
cation of PFO especially useful for device
planning are summarized in . Fig. 1 and
. Tables 2 and 3.
PFO and stroke
The new updated neurological defini-
tion describes stroke as an acute episode
of focal dysfunction of the brain, retina
Herz 5 · 2021 445
 Main topic

Table 1 American Society of Echocardiography (ASE) [21] proposed definitions system through the PFO into the arte-
Patent foramen ovale Right-to-left shunt (RLS) of blood demonstrated by Doppler or saline rial circulation and occluded the cerebral
(PFO) contrast injection without a true deficiency of the interatrial septum (IAS) artery [32]. Litten made a similar report
Stretched PFO with Stretched open by atrial hemodynamics, creating a defect in the septum in 1880, in a patient with stroke and PFO
left-to-right shunt causing left to right shunt [33, 34].
(LRS)
In up to 25% of all cases, the cause
Atrial septal aneurysm Excursion of the septal tissue (typically the fossa ovalis) of greater than
of stroke remains unknown and these
(ASA) 10 mm from the plane of the atrial septum into the right atrium (RA) or
left atrium (LA) are designated as cryptogenic stroke
[35]. By now, several studies have shown
the ability of a venous thrombus to
Table 2 Comparison of TTE vs TEE for the diagnostic evaluation of PFO. (Modified from Filomena migrate through a PFO into the ar-
et al. 2021 [61])
terial circulation [36, 37]. In the last
Diagnostic Advantage Disadvantage
modality:
few years, there have been six studies
focusing on closure of a PFO com-
TTE Recognition of RLS with a Inadequate anatomical evaluation
–Sensitivity 88% for procedural planning pared to medical therapy (antiplatelet
–Specificity 82% Not reliable for small shunts or oral anticoagulants [OAC]). Ini-
–AUC 0.91 Possibility of false positive due to tially, three studies (CLOSURE-I, PC-
Well tolerated. intrapulmonary shunt Trial, RESPECT) with intermediate-term
Low cost, widely available
follow-up showed no significant reduc-
Adequate elevation of RA pressure with Val-
salva maneuver tion of recurrent stroke by PFO closure
Reasonable initial screening test compared to optimal medical therapy
TEE Gold standard for searching SOE: Costly (OMT) [38–40]. Three additional studies
–Sensitivity 89% Patient discomfort (in 2017 and 2018), CLOSE, REDUCE
–Specificity 91% Sometimes inadequate Valsalva and DEFENSE—PFO showed a signif-
–AUC 0.93 maneuver icant reduction in recurrent stroke in
Detailed anatomical evaluation of PFO Although rare but important com-
Reasonable for procedural planning plications
the PFO closure group [1–3]. When the
Exclusion of associated copathologies follow-up of the RESPECT study was
AUC Area under the curve, SOE Source of embolism, RLS Right to left shunt, PFO Patent foramen ovale, prolonged up to 6 years, the investigators
TTE transthoracic echocardiogram, TEE transesophageal echocardiogram, RA right atrium also found a significant reduction in the
PFO closure group [41]. The CLOSE
study even compared subgroups of drug
or spinal cord persisting for more than new strokes worldwide, an increases first therapy, antiplatelets vs OAC (vitamin K-
24 h or any duration if imaging (com- stroke incidence of 68% and all stroke-re- antagonist with INR 2–3), and showed
puted tomography [CT]/magnetic reso- lated deaths increased also by 26% (2010 no significant difference in reduction of
nance imaging [MRI]) or autopsy show vs 1990). Most causes were ischemic stroke recurrence in the medical ther-
a corresponding infarction or hemor- and hemorrhagic stroke, which showed apy arms [42]. If the results of all six
rhage [24]. Strokes are divided into is- an increase in incidence by 37% and 47%, studies are combined, it shows a 75%
chemic and hemorrhagic strokes [25]. respectively [27, 28]. reduction of recurrent stroke in patients
The ischemic stroke is further classified Each year about 243,000–260,000 in- under 60 years of age with a PFO (with
into five categories by using the TOAST dividuals suffer a stroke in Germany [29] a moderate-to-large and large right-
classification system [26]: large artery with an estimated incidence of 365 new to-left shunt) [43]. Several systematic
atherosclerosis, small artery occlusion, cases per 100,000 individuals [30]. The meta-analyses revealed that PFO closure
cardioembolism, stroke of other deter- risk of recurrence is high; an analysis of reduces the risk of ischemic stroke in pa-
mined and undetermined etiology. In the Erlangen Stroke Registry showed a re- tients with PFO and cryptogenic stroke
the cardioembolism category, sources are currence of 15% within a 2-year follow- [44–46].
divided into high-risk and medium-risk up [31].
sources. Medium-risk sources are mi- Current guidelines
tral annulus calcification, atrial septal PFO-associated stroke
aneurysm, and PFO [26]. Based on these study results, current Ger-
Stroke is the second leading cause The first to describe a possible correla- man guidelines of three major societies
of death worldwide, following ischemic tion of a PFO and stroke was Cohnheim (Deutsche Gesellschaft für Neurologie
heartdisease [27]. The numberofstrokes, in 1877. A young patient was diagnosed [DGN], Deutsche Gesellschaft für Kar-
survivors of stroke, disability-adjusted on autopsy with a closure of a cerebral diologie [DGK], Deutsche Schlaganfall-
life–years lost due to stroke and stroke- artery and a PFO so that Cohnheim pos- Gesellschaft [DSG]) recommend per-
related deaths is increasing [28]. Between tulated that a blood clot from the periph- forming closure of a PFO in patients
1990 and 2010 there were 16.9 million eral veins had travelled from the venous aged 16–60 years with prior cryptogenic

446 Herz 5 · 2021


ischemic attack (level of recommenda-
tion A, class of evidence I; according to
the AWMF criteria [47]) [43]. Notably,
it has also been shown that patients
younger than 55 years of age with a PFO
are at increased risk of suffering crypto-
genic ischemic stroke [48].
The RoPE score is a good method
to estimate the role of PFO in crypto-
genic stroke. The RoPE score includes
several established risk factors of stroke
such as age, hypertension, hypercholes-
terolemia and diabetes mellitus, the ab-
sence of a prior stroke and the presence
of a superficial infarct [49].
After PFO closure, antithrombotic
therapy is recommended with acetylsali-
cylic acid (ASA; 100 mg) and clopidogrel
(75 mg) for 1–3 months and subsequently
a monotherapy with ASA or clopidogrel
for 12–24 months. If the patient has
other atherosclerotic diseases, lifelong
monotherapy is recommended (level of
recommendation B, class of evidence IIb)
[43]. Furthermore, the guidelines sug-
gest using a disc occluding device since
it has been proven to be safer and more
effective than noncircular disc-shaped
occluding devices (level of recommen-
dation A, class of evidence Ia) [43].
Complications during the interventions
are so rare that they should not influ-
ence the decision of PFO closure (level
of recommendation A, class of evidence
Ia) [43]. For patients who refuse the im-
plantation of a PFO occluder, there is no
evidence that an anticoagulation strategy
is better than antithrombotic therapy.
Thus, those patients should receive a sec-
ondary prevention strategy with ASA or
clopidogrel (level of recommendation B,
class of evidence IIb) [43].
PFO and decompression
sickness
Although data suggest a role of PFO in
decompression sickness (DCS) in divers
and high-altitude pilots [5], screening
for PFO should not be carried out on
a routine basis. Only for highly selected
cases, e.g., high-risk divers with high-risk
work activity or military pilots flying in
very high altitudes can primary screening
be useful in order to primarily close the
PFO.
Abstract · Zusammenfassung
Herz 2021 · 46:445–451 https://doi.org/10.1007/s00059-021-05061-y
© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2021
A. Maloku · A. Hamadanchi · M. Franz · G. Dannberg · A. Günther · C. Klingner · P. C. Schulze ·
S. Möbius-Winkler
Patent foramen ovale—When to close and how?
Abstract
Closure of a patent foramen ovale (PFO) in
patients after cryptogenic/cardioembolic
stroke is recommended by current guidelines
for patients who are 16–60 years of age with
a high-risk PFO (class of recommendation A,
level of evidence I). The use of double-disk
occlusion devices followed by antiplatelet
therapy is recommended. The procedure of
interventional PFO closure compared with
other interventions in cardiology is rather easy
to learn. However, it should be performed
carefully to avoid postinterventional
complications. The number needed to treat
(NNT) to avoid one stroke in 5 years in the
RESPECT trial was 42, in the CLOSE trial even
Offenes Foramen ovale – wann und wie soll es verschlossen
werden?
Zusammenfassung
Der Verschluss eines offenen Foramen
ovale (PFO) wird für Patienten nach kryp-
togenem/kardioembolischem Schlaganfall
im Alter zwischen 16 und 60 Jahren
in den aktuellen Konsensusleitlinien
mehrerer Fachgesellschaften empfohlen
(Empfehlungsklasse A, Evidenzlevel I).
Die Anwendungen eines sog. Double-
Disc-Okklusionssystems wird präferenziell
empfohlen. Die interventionelle Technik
des PFO-Verschluss ist, verglichen mit
anderen interventionellen Eingriffen in der
Kardiologie, einfach zur erlernen, sollte
aber mit größter Vorsicht zur Vermeidung
von periinterventionellen Komplikationen
vorgenommen werden. Die „number needed
to treat“ (NNT), um ein Schlaganfallrezidiv in
5 Jahren zu verhindern, lag in der RESPECT-
After a DCS, behavioral and technical
changes must be made first. Then, if not
possible or not effective, a PFO closure
can be considered. It must be done under
shared decision making, acknowledging
the lack of evidence [5].
PFO and migraine
Several observational studies were able to
show an association of migraine with aura
and PFO [50–53]. There are currently
randomized trials and several registries
lower with 20. In the REDUCE trial, the NNT
was 28 at 2 years. This can be reduced by
longer follow-up, e.g., at 10 years the NNT is
18. While other conditions such as migraine
are currently under investigation with respect
to the impact of PFO closure, sufficiently
powered trials are lacking so that closure in
diseases other than stroke should always be
individualized.
Keywords
Platelet aggregation inhibitors · PFO-
associated stroke · Secondary prevention ·
Cryptogenic ischemic stroke · Migraine
Studie bei 42, in der CLOSE-Studie sogar bei
nur 20. In der REDUCE-Studie war die NNT
28, um ein Schlaganfallrezidiv in 2 Jahren zu
verhindern. Mit längerer Beobachtungszeit
reduziert sich die NNT weiter, z. B. nach
10 Jahren auf 18. Viele andere Krankheiten,
wie Migräne, sind Gegenstand der Forschung
als potenzielle Ziele für den PFO-Verschluss;
aktuell fehlen aber ausreichend gepowerte
Studien, sodass der Verschluss bei anderen
Krankheiten von Fall zu Fall entschieden
werden sollte.
Schlüsselwörter
Thrombozytenaggregationshemmer ·
Foramen-ovale-bedingter Schlaganfall · Se-
kundärprävention · Kryptogener ischämischer
Schlaganfall · Migräne
with contradictory results analyzing the
role of PFO closure in this population.
A recent meta-analysis of 7 studies was
able to demonstrate a significant reduc-
tion of migraine attacks after PFO clo-
sure compared to controls in included
randomized trials as well as in registries
[54]. However, there is currently no rec-
ommendation for PFO closure in mi-
graine patients outside of clinical trials
or in very selected cases as a compas-
sionate use strategy.
Herz 5 · 2021 447
 Main topic
PFO and arterial deoxygenation
syndromes
Several case reports for platypnea–orth-
odeoxia syndrome (POS) [55, 56] and
case controls of obstructive sleep apnea
syndrome (OSAS) [57] have shown the
448 Herz 5 · 2021
Fig. 2 9 Examples
of available double
disc patent foramen
ovale (PFO) occlud-
ing devices
potential of PFO closure to impact ar-
terial oxygen saturation and symptom
relief in selected patients. However, ran-
domized studies are lacking. Currently,
the consensus is against routine closure
of PFO in these conditions [5].
Fig. 1 9 Different forms
of complex PFO. EV Eu-
stachian valve, PFO Patent
foramen ovale, RA right
atrium, LA left atrium
PFO and other conditions
Currently, there are data suggesting
a potential role of PFO in several other
conditions including stroke during preg-
nancy, perioperative stroke in noncardiac
surgery, and neurosurgery in the sitting
position [5]. Nevertheless, hard evidence
is missing and prospective studies must
be performed.
PFO occluders
Interventional closure of a PFO was
first reported in 1987 [58]. Since
then, several different devices usu-
ally double umbrella occluders have
been developed. Initial experience
®
with devices (ASDOS [Sulzer Osypka,
®
Germany], CardioSEAL , StarFLEX ®
[both NMT Medical Inc. Boston, MA,
®
USA], PFO-Star [Cardia, Burnsville,
®
MN, USA], Helex [W.L. Gore and
Associates, Flagstaff, AZ, USA], An-
®
gel Wings [Microvena, Vadnais, MN,
®
USA], Amplatzer [AGA Medical Golden
Valley, CA, USA]) showed elevated risk
for device-induced atrial fibrillation and
elevated thrombogenicity [59]. The cur-
rent, second generation of devices was
introduced in 1997 with the Amplatzer
Table 3 Pitfalls of echocardiographic diagnosis stability while pushing against the PFO
Pitfall Reason Solution channel and facilitates passage.
False Inadequate elevation of Using other contrast agents like dextrose-containing Once the left atrium is instrumented,
neg- RA pressure by Valsalva solutions and other commercial available options (e.g. a bolus injection of 100 IU heparin/kg
ative maneuver ®
Echovist [Bayer Vital,Leverkusen, Germany], Haemacell ® bodyweight is administered (target ac-
bubbles Inadequate dense opaci- ®
[Piramal Healthcare UK limited, UK], Gelifundol [B.Braun,
tivated clotting time around 250 s) and
test fication/filling of RA by Melsungen, Germany])
contrast material Elevation of forearm + abdominal pressure during the the left atrial pressure (LAP) should be
Wash out phenomenon by injection measured. If the LAP is below 5 mm Hg,
IVC flow Avoidance of contrast study in fully sedated ventilated the likelihood of breathing-associated air
patients embolism through the catheter is elevated
When very prominent IVC wash-out phenomenon: injec-
and IV fluid should be given to reach
tion from a lower extremity vein
a mean LAP of 5–10 mm Hg.
Late Atypical PFO Increase intraabdominal pressure
appear- Pulmonary AV fistula The MP catheter is then advanced into
ance of the LA under TEE guidance aiming at the
contrast left upper pulmonary vein. A long stiff
in LA guidewire with a soft tip (e.g., Amplatz
Atypical Multifenestrated septum Complete scanning of IAS using color Doppler with a low super stiff 260 cm, Boston Scientific) is
mor- ± ASA Nyquist limit (35–45 cm/s) advanced over the MP catheter and the
pholo- Multiple small ASDs associ- 3D imaging of the septum
gies ated with PFO
catheter exchanged for a 24 mm sizing
balloon. Of note, balloon sizing of the
RA Right atrium, LA Left atrium, IVC Inferior vena cava, ASD Atrial septal defect, IAS Interatrial septum, PFO is also controversial. From our per-
ASA Atrial septal aneurysm, AV Atrioventricular, PFO Patent foramen ovale, 3D three dimensional spective, PFOs and especially tunneled
PFOs are highly variable in size and bal-
loon sizing helps to choose the adequate
PFO occluder, a nitinol-based double (preferably through an arterial line) is device size by maximizing the septal de-
disc occlusion device [60]. Since then, needed. hiscence. The measurement will be done
several new devices have been devel- The procedure is done via femoral ve- in two perpendicular echo projections
oped but the double disc structure is still nous access usually from the right side of (e.g., 45 and 135°) and is confirmed by
the design of choice in most products. the patient. After puncture, a standard sizing on the angiography images using
. Figure 2 shows a selection of devices wire (J-tip) and a sheathless 5 Fr mul- the smallest balloon tail for measuring.
currently used and approved for the tipurpose (MP) catheter is introduced. An adequately sized closure de-
European market. The right atrial pressure should be mea- vice—according to the instruction for
sured to document a normal central ve- use—is then prepared. A sheath (e.g.,
Procedural aspects of PFO nous pressure of 6–12 mm Hg. If lower, Mullins sheath) is used (usually between
closure at least 500 ml saline should be adminis- 7 and 9 Fr) depending on device size
tered. The wire is advanced via the PFO and manufacturing company. The siz-
Device implantation is performed in by pushing it against the atrial septum ing balloon is deflated and exchanged
a standard cardiac catheterization lab- (superior) and it usually slides through against the sheath. After aspiration of
oratory using usually fluoroscopy, TEE easily. Occasionally, the support of the blood, a wet-to-wet connection of the
guidance and physiological monitoring. MP catheter is needed to guide the wire sheath and the device delivery system
There is an ongoing controversy whether into the inferior atrial region. In rare guarantees a bubble-free advancement
TEE guidance is needed but interven- cases, especially in narrow and tunneled of the device. The device is then pushed
tionalists are using nearly exclusively PFOs, it can be difficult to pass through, into the sheath, the sheath is pulled back
TEE for procedural guidance to avoid so the support of TEE imaging can be into the mid left atrium and the left-
radiation in younger patients. It is rec- helpful to guide the wire and catheter into sided disk is expanded. This can be
ommended using a combination of both the fossa ovalis. The optimal visualization done completely radiation free under
imaging methods to have the greatest by TEE is atrial visualization with sweep- echocardiographic guidance. The left-
amount of imaging information available ing from 30–90°. Angiographically, this sided disk is then pulled back against
while having radiation exposure as low as is usually done in an anterior–posterior the interatrial septum under echocardio-
possible. Disadvantages of this method view. It can be helpful to rotate to a 45° graphic control until a weak resistance is
is the need for conscious sedation during left anterior oblique (LAO) view. In dif- felt. Under discrete tension, the sheath
the procedure for better TEE tolerance. ficult cases, a small amount of contrast is pulled back over the device to expand
A peripheral line is needed for fluid medium can be administered to help lo- the right-sided disk. If this is done,
infusion and medication for sedation cate the PFO. In narrow PFO channels, it the device is gently pushed against the
(midazolam and propofol). Monitoring can be helpful to use a transseptal sheath septum until the disk is closed.
of O2 saturation and arterial pressure with a transseptal needle to gain more

Herz 5 · 2021 449

 Main topic
Echocardiography now has to prove
the correct position of the device. Angio-
graphically the so-called packman sign
helps to see the correct position. The
edges of the device should be carefully
inspected to avoid interaction of the discs
with the LA roof or the aorta to avoid
localized compression damage. Once the
device is in correct position it can be re-
leased, and the delivery system and the
sheath can be retracted. Closure of the
femoral vein can be done by a Z-suture of
the subcutaneous tissue or via a Proglide
(Abbott) closure device.
After the patient is fully awake, a neu-
rological checkup is performed. Mon-
itoring of blood pressure and heart
rate should be performed for 24 h. To
avoid thrombus formation on the left
atrial disc, our standard is to administer
heparin to the patients for up to 24 h.
However, this may be shortened based
on clinical individual practice since there
is no evidence to support this strategy.
A dual antiplatelet therapy for up to
3 months followed by ASA alone for up
to 9–21 months is recommended by the
guidelines [43]. However, evidence for
this recommendation is not based on
randomized evidence.
Complications during and after PFO
closure placement are relatively rare and
include access site complications such as
hematoma, AV shunt, neurological com-
plications like air embolism, stroke and
TIA (transient ischemic attack), pericar-
dial effusion/tamponade and device-as-
sociated atrial fibrillation [1–3, 38–40].
Pericardial tamponade occurred rarely in
the RESPECT and REDUCE trial at a rate
of 0.4% and 0.2%, respectively [3, 38]. In
the other trials, no postprocedural peri-
cardial effusion was seen. Cardiac per-
foration was a severe complication that
occurred in 0.25% in the CLOSURE-I
trial and in 0.2% in the RESPECT trial
[1, 58]. Transient postprocedural atrial
fibrillation/flutter occurred in all trials
ranging from 0.5–5.4%. It seems that
some devices are more likely to induce
atrial fibrillation than others. Device-as-
sociated thrombus occurred in 0–1.1% of
cases. Bleeding as complication ranged
from 0–2.5% [1–3, 38, 39, 49].
450 Herz 5 · 2021
Conclusion
Interventional closure of a patent fora-
men ovale (PFO) is a safe and established
procedure and should be routinely per-
formed in patients aged between 16 and
60 years with cryptogenic ischemic stroke
and detection of a PFO.
Corresponding address
Sven Möbius-Winkler
Department of Internal Medicine I, Cardiology,
Angiology, Intensive Medical Care, University
Hospital Jena
Am Klinikum 1, 07747 Jena, Germany
Sven.Moebius-Winkler@med.uni-jena.de
Declarations
Conflict of interest. A. Maloku, A. Hamadanchi,
M. Franz, G. Dannberg, A. Günther, C. Klingner,
P. C. Schulze and S. Möbius-Winkler declare that they
have no competing interests.
For this article no studies with human participants
or animals were performed by any of the authors. All
studies performed were in accordance with the ethical
standards indicated in each case.
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