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Incidental PFO: To close or not to close?
Joseph P. Mathew, MD
A patent foramen ovale (PFO) results from persistence of the interatrial communication at
the site of the embryonic ostium secundum. In the fetus, blood from the inferior vena cava
is directed toward the foramen ovale by the Eustachian valve, passing ultimately from the
right atrium to the left atrium. The right atrial aspect of the foramen ovale is characterized
by a muscular rim, whereas the left atrial aspect is flat with a crescent-shaped opening. At
birth, as left atrial pressures increase, the overlap of the septum primum against this rim
closes the foramen ovale. Over the next year of life, the flap of the septum primum and the
rim become more adherent resulting in complete closure. However, autopsy findings have
reported that the foramen ovale remains probe-patent in 25-35% of patients.1 Since the flap
created by the ostium secundum is larger than the fossa, the length of the overlap can be
substantial and result in a tunnel-like opening. In one small study, Ho et al2 demonstrated
tunnel lengths of 1–6 mm and widths of 5–13 mm along the curve of the rim.
Based on their experience with transcatheter closure of a PFO, Rana et al3 have proposed
that PFOs can be categorized as either simple or complex. A simple PFO is a standard PFO
with tunnel length <8 mm, without an atrial septal aneurysm, without a large Eustachian
ridge or valve, without a thickened (< 10 mm) septum secundum, and without other defects
of the fossa ovalis. A complex PFO, on the other hand, is one that has any of the following
characteristics: 1) PFO with a long tunnel length (>8 mm) 2) Multiple openings of the PFO
on the left atrial side 3) Atrial septal aneurysm defined as mobility of the septum > 10 mm
in either direction 4) Hybrid defect - the concomitant occurrence of a PFO with additional
defects on the fossa ovalis 5) Excessive thickening (> 10 mm) of septum secundum 6)
Presence of Eustachian ridge 7) Presence of Eustachian valve (or Chiari network).
Detection of an intra-atrial shunt is a prerequisite for the diagnosis of a PFO. While
different imaging modalities including transcranial Doppler, intracardiac
echocardiography, and transthoracic echocardiography have been used to detect a right-toleft shunt, a transesophageal echo (TEE) bubble study remains the gold standard for
diagnosing PFO. In one meta-analysis that included 164 patients, TEE had a sensitivity of
89.2% (95% CI: 81.1-94.7%) and specificity of 91.4% (95% CI: 82.3-96.8%) to detect
PFO.4 TEE evaluation of the foramen ovale should include two-dimensional assessment
for flap movement and color-flow Doppler assessment, optimized for measurement of
lower velocity flow. Injection of agitated saline (a “bubble study”) along with a Valsalva
maneuver is typically used to provoke right to left shunting. In such a study, the bubbles
should be injected after the Valsalva maneuver produces a decrease in right atrial volume,
and the Valsalva should be released (so as to transiently increase right trial pressure over
left atrial pressure) when the microbubbles are first seen to enter the right atrium.
Admixture of agitated saline with small quantities of blood has been reported to improve
the acoustic signal of the microbubbles. The bubble study is positive if bubbles appear in
the left atrium within five cardiac cycles.
Multiple complications have been associated with a PFO.5 Of these, the increased
incidence of PFO in younger patients with cryptogenic stroke has garnered the greatest
attention. In a meta-analysis of 1024 patients, the odds ratio for the presence of a PFO in
cryptogenic stroke in individuals < 55 years of age was 3.1 (95% CI 2.3–4.2).6 On the
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basis of multiple reports demonstrating a thrombus in transit between the right and left
atrium through a PFO, it is commonly assumed that paradoxical embolization is the cause
of the increased incidence of cryptogenic stroke.5 However, other mechanisms of embolic
stroke in association with a PFO have been proposed including alterations in atrial function
similar to those in patients with chronic atrial fibrillation. 7 These abnormalities were more
pronounced in those with moderate to large atrial septal aneurysms who in turn were noted
to be more likely to have coagulation abnormalities and spontaneous left atrial contrast.
Furthermore in patients with PFO and cryptogenic stroke, the incidence of atrial fibrillation
(a risk factor for stroke) ranges from 8–15%.8
An association between PFO and migraine was highlighted when patients who had a PFO
closed for other reasons reported an improvement in the frequency and severity of
migraine headaches.9 A meta-analysis of 2636 subjects reported an odds ratio of 5.13 (95%
CI 4.7–5.6) but concluded that there was only low grade evidence to support the
association between migraine and PFO.10 The only randomized trial of device closure in
patients with migraine failed to demonstrate a clear benefit.11,12 Decompression illness in
scuba divers is another arena where a PFO may play a critical role. Torti et al13
investigated 230 scuba divers and reported that PFO was present in 23% and was
associated with an increased risk of a significant decompression event.
The platypnea–orthodeoxia syndrome is characterized by dyspnea and hypoxemia upon
standing up. The symptoms are thought to occur because standing upright causes inferior
vena cava inflow redirection towards the inter-atrial septum and therefore, increased
shunting through a PFO. The syndrome is typically seen after a right pneumonectomy
where the cardiac position is shifted in a manner that increases flow toward the PFO.14
Redirection of inferior vena caval flow towards the inter-atrial septum has also been
reported in patients with an enlarged or “horizontalized” aortic root. In this case, the flow
alteration is a consequence of the cardiac rotation that distorts atrial septal position.15
Perioperatively, in addition to the reports of systemic embolism, hypoxemia due to
shunting through a PFO has been described,16 particularly in those with elevated right
atrial pressures (e.g. pulmonary hypertension, right ventricular failure) and/or reduced left
atrial pressures (e.g. left ventricular assist device).
The intraoperative detection of a previously undiagnosed PFO creates a quandary for the
surgical and anesthesia care teams. Sukernik and Bennett-Guerrero concluded that “there is
general agreement that a PFO should be closed when development of a significant right-toleft shunt after surgery is highly likely”.17 Two instances where closure is strongly
recommended are with the insertion of a left ventricular assist device (unloaded left
ventricle lowers right atrial to left atrial pressure gradient and can increase shunting) and
with heart transplantation (elevated pulmonary vascular resistance increases right atrial
pressures). Surgical closure was also recommended when atriotomies were planned as part
of the scheduled surgical procedure although there is no data to specifically support such a
strategy. In all other cases, the authors recommended that closure be considered when the
risk was increased as defined by a large PFO, a history of paradoxical embolization,
interatrial septal aneurysm, history of professional diving, or a right to left shunt (including
from luxation of the heart during off-pump surgery).17,18 The rationale here is that the risk
of an altered cannulation scheme and prolonged cardiopulmonary bypass time is
minimal.19 On the other hand, the typical cardiac surgery patient is elderly and
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atherosclerosis and atrial fibrillation are more likely sources of embolism. Thus, an
argument can be made that there would be minimal benefit to routinely closing the PFO in
older patients without right ventricular overload.18 Furthermore, instituting
cardiopulmonary bypass in an off-pump procedure could substantially increase patient risk.
In a survey of national surgical practice conducted in 2002, the majority of surgeons
decided to close an incidental PFO if the PFO was large, if right atrial pressure was
elevated or if there was a history of paradoxical embolism.20 Interestingly, during surgery
with cardiopulmonary bypass, 28% always closed the PFO while 10% never chose to close
the PFO. In off-pump surgery, 28% never altered the surgical plan while 11% always
converted to on-pump surgery in order to repair the PFO. A large majority (73%) reported
never experiencing a PFO-related complication in the immediate postoperative period that
then required additional intervention.
To address the impact on PFO repair upon outcomes, Krasuski et al21 evaluated 13,092
cardiac surgical patients without a history of PFO or atrial septal aneurysm. An incidental
PFO was diagnosed intraoperatively in 17% and after propensity matching, postoperative
stroke or mortality was not different in patients with and without a PFO. Twenty eight
percent of the PFO patients had their PFO closed as part of the surgical procedure with
closure more likely in younger patients, those undergoing mitral or tricuspid valve surgery,
and those with a history of transient ischemic attack or stroke. PFO repair did not offer a
long-term survival advantage but was associated with a 2.5 times greater odds of
postoperative stroke. This increased risk of stroke is not readily explained since the
cardiopulmonary bypass time increased only by a mean of 6 minutes.
In addition to primary surgical closure, medical management with anticoagulation/
antiplatelet medications and percutaneous closure may also be considered. In a recent
systematic review, the risk of recurrent transient ischemic attack or stroke with device
closure was 1.3% compared to 5.2% with medical treatment.22 Although the rate of major
complications with percutaneous closure is low at 1.5-2.3%, death, hemorrhage,
emergency surgery, tamponade, and pulmonary embolism are possibilities. Other
complications include atrial fibrillation which is higher following device closure and may
be related to the size of the device. Incomplete PFO closure has also been reported in 20%
undergoing device closure with 14% demonstrating large residual shunts.5
The American Heart Association/American Stroke Association has published guidelines
that support the use of antiplatelet or warfarin therapy for high-risk patients with other
indications such as hypercoagulable state or venous thrombosis.23 Evidence to recommend
device closure for a first stroke is insufficient but PFO closure may be considered for
recurrent cryptogenic stroke on optimal medical treatment. Although management
strategies for an incidental PFO discovered during surgery are not addressed by these
guidelines, closure is recommended during heart transplantation and left ventricular assist
device placement. It is also reasonable to consider closure in patients with a large PFO, a
history of paradoxical embolization, interatrial septal aneurysm, history of professional
diving, or a right to left shunt. However, the increased risk of postoperative stroke with no
clear survival advantage of repair should be considered in the risk-benefit analysis.
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