Some Air for Closure of the Patent Foramen Ovale*

JACC: CARDIOVASCULAR INTERVENTIONS
© 2012 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER INC.
VOL. 5, NO. 4, 2012
ISSN 1936-8798/$36.00
DOI: 10.1016/j.jcin.2012.02.008
EDITORIAL COMMENT
Some Air for Closure of the
Patent Foramen Ovale*
Bernhard Meier, MD
Bern, Switzerland
The patient is 56 years old. He likes sports, in particular
deep-sea diving. After 2 decompression incidents, he was
worked up by a cardiologist and a patent foramen ovale
(PFO) was found. Incidentally, he mentioned that he has
been increasingly short of breath during physical exercise.
The PFO was closed (Fig. 1) in an outpatient procedure,
and the next day, already, he enjoyed an improved exercise
capacity when jogging. This effect proved to be sustained
and diving has remained uneventful since.
See page 416
It has been known but hardly discussed that a PFO can not
only produce systemic arterial desaturation in elderly people
sitting upright (platypnea-orthodeoxia) but also during exercise
as in the patient described. What has not been known but is
nicely shown by Devendra et al. (1) in this issue of JACC:
Cardiovascular Interventions is that it may do so much more
commonly than previously thought. The investigators found
provoked exercise desaturation in every third patient. This
percentage depends heavily on the indications for PFO closures and the referral pattern and appears much smaller in our
personal experience. Nonetheless, it adds to the already lengthy
list of possible indications for PFO closure (Table 1).
The focus around PFO closure has always concentrated too
much on patients with prior stroke or transient ischemic
attacks. Notwithstanding, these are the most devastating problems a PFO can mediate and their issue may be lethal.
However, paradoxical myocardial infarction may also bring
about death and severe disability.
The reticence to implant a device into the middle of the heart
just for preventive reasons is understandable and has recently grown when the results of the yet unpublished
CLOSURE I (A Prospective, Multicenter, Randomized,
Controlled Trial to Evaluate the Safety and Efficacy of the
*Editorials published in JACC: Cardiovascular Interventions reflect the views of the
authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
From the Cardiovascular Department, Bern University Hospital, Bern, Switzerland. Dr. Meier has received research grants from and has served on the Speaker’s
Bureau of St. Jude Medical.
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STARFlex Septal Closure System vs. Best Medical Therapy in
Patients with Stroke or Transient Ischemic Attack due to
Presumed Paradoxical Embolism through a Patent Foramen
Ovale) trial failed to prove an advantage of PFO closure over
medical therapy during the first 2 years of follow-up. This may
change should one or both of the controlled randomized trials
on that topic that are expected to be published next meet their
primary endpoints of superiority of PFO closure over medical
treatment. The PC-Trial (Patent Foramen Ovale and Cryptogenic Embolism) (NCT00166257) (2) is in the analysis
phase and encompasses roughly 400 patients followed-up for a
minimum of 2 and a maximum of 10 years. The RESPECT
(Randomized Evaluation of Recurrent Stroke Comparing
PFO Closure to Established Current Standard of Care Treatment) trial (NCT00465270) is about to be analyzed with a
comparable follow-up duration in about 1,000 patients. Both
trials exclusively used Amplatzer PFO occluders (St. Jude
Medical, St. Paul, Minnesota), representing the state-of-theart devices. Meanwhile, the results of a propensity matched
analysis of about 300 patients with either PFO closure using a
variety of devices or medical treatment and a median follow-up
of about 10 years supports the procedure by showing even a
mortality benefit when comparing follow-up years with a
closed PFO to those with an open PFO (3).
To place a device into the heart for therapeutic reasons is
a much more palatable situation as witnessed in the realm of
interventional cardiology with coronary stenting and percutaneous valve replacement. The migraine indication has lost
steam secondary to the negative MIST (Migraine Intervention with STARFlex Technology) trial (4). Yet, PFO
closure does tame migraine symptoms in real life (5).
Closing a PFO for platypnea-orthodeoxia is an uncontested
but rare indication. The opposite is true for closing a PFO
for sleep apnea. Now we do have the newcomer, provoked
exercise desaturation. I suggest that we look for a PFO in
patients complaining about unexplained exertional dyspnea
and to close it when present, crossing our fingers that the
symptoms will improve. If they do not, the patient will still
enjoy the collateral benefit of not being at risk any longer for
paradoxical embolism be it to the brain, the heart, or
elsewhere. Leaving the PFO open means missing the
chance of symptom improvement and leaving the patient
exposed to rare but serious risks for the rest of his or her life,
well aware of the fact that these risks increase with age in
parallel to the increase of venous thrombosis (6). Should we
go as far as to test symptomatic PFO carriers for provoked
exercise desaturation as described by Devendra et al. (1)?
Probably not, as we usually have a more compelling indication at hand.
We are indebted to Devendra et al. (1) for opening our
eyes to a fact that was there all the time but was just
overlooked. Their original and insightful study on a small
group of patients with a particular medical situation may
help to open the door to what some day may become some
Meier
Editorial Comment
JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 5, NO. 4, 2012
APRIL 2012:420 –1
Frontal
421
Lateral
TEE FU at 9 mo
Perfect result
LA
Furrer Fredy, 07.03.1955, 11.04.2011, 05.01.2012
RA
LA
LA
LA
SS
SP
RA
RA
RA
Figure 1. Right-to-Left Shunt Through a PFO
Right-to-left shunt through a patent foramen ovale (PFO) (dashed arrow) demonstrated by contrast medium injection into the right atrium (RA) in the frontal
and lateral projections. The bottom inset shows the immediate result after closure of the PFO with a 25-mm Amplatzer PFO occluder (St. Jude Medical, St. Paul,
Minnesota) and the top inset shows the complete tightness at the 9-month follow-up (FU) transesophageal echocardiogram (TEE). LA ⫽ left atrium; SP ⫽ septum primum; SS ⫽ septum secundum.
Table 1. Possible Indications for PFO Closure
Secondary prevention
kind of a PFO closure campaign. For the time being, their
study gives PFO closure some direly needed but welldeserved air.
Stroke
Transient ischemic attack
Embolic myocardial infarction
Peripheral embolism
Reprint requests and correspondence: Dr. Bernhard Meier,
Cardiovascular Department, University Hospital Bern, 3010 Bern,
Switzerland. E-mail: [email protected].
Compression incident
Primary prevention
Aggravating PFO attributes
Atrial-septal aneurysm
Eustachian valve
Chiari network
Deep vein thrombosis
Pulmonary embolism
Embolism-prone surgery
Major orthopedic
Cerebral in sitting position
Planned pregnancy
Therapeutic
Migraine
Platypnea-orthodeoxia
Sleep apnea
Provoked exercise desaturation
Vocational or recreational
Deep-sea diver
Brass musician
Glass blower
Military jet pilot or astronaut
Commercial driver or pilot
PFO ⫽ patent foramen ovale.
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REFERENCES
1. Devendra GP, Rane AA, Krasuski RA. Provoked exercise desaturation
in patent foramen ovale and impact of percutaneous closure. J Am Coll
Cardiol Intv 2012;5:416 –9.
2. Khattab AA, Windecker S, Jüni P, et al. Randomized clinical trial
comparing percutaneous closure of patent foramen ovale (PFO) using
the Amplatzer PFO occluder with medical treatment in patients with
cryptogenic embolism (PC-Trial): rationale and design. Trials 2011;12:56.
3. Wahl A, Jüni P, Mono ML, et al. Long-term propensity-score matched
comparison of percutaneous closure of patent foramen ovale with medical
treatment after paradoxical embolism. Circulation 2012;125:803–12.
4. Dowson A, Mullen MJ, Peatfield R, et al. Migraine Intervention with
STARFlex Technology (MIST) trial: a prospective, multicenter,
double-blind, sham-controlled trial to evaluate the effectiveness of patent
foramen ovale closure with STARFlex septal repair implant to resolve
refractory migraine headache. Circulation 2008;117:1397– 404.
5. Wahl A, Praz F, Tai T, et al. Improvement of migraine headaches after
percutaneous closure of patent foramen ovale for secondary prevention of
paradoxical embolism. Heart 2010;96:967–73.
6. Anderson FA Jr., Wheeler HB, Goldberg RJ, et al. A population-based
perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism. The Worcester DVT study. Arch
Intern Med 1991;151:933– 8.
Key Words: closure of patent foramen ovale 䡲 dyspnea 䡲
paradoxical embolism 䡲 platypnea-orthodeoxia.

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