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[9] Steiner MM, Di Tullio MR, Rundek T, et al. Patent foramen ovale size and embolic brain imaging findings among patients with ischemic
stroke. Stroke 1998;29:944e8.
[10] Homma S, Di Tullio MR, Sacco RL, Mihalatos D, Li Mandri G, Mohr JP. Characteristics of patent foramen ovale associated with cryptogenic
stroke. A biplane transesophageal echocardiographic study. Stroke 1994;25:582e6.
[11] Hausmann D, Mugge A, Daniel WG. Identification of patent foramen ovale permitting paradoxic embolism. J Am Coll Cardiol 1995;26:
1030e8.
[12] Goel SS, Tuzcu EM, Shishehbor MH, et al. Morphology of the patent foramen ovale in asymptomatic versus symptomatic (stroke or transient
ischemic attack) patients. Am J Cardiol 2009;103:124e9.
[13] Murray G. Closure of defects in cardiac septa. Ann Surg 1948;128:843e53.
[14] King TD, Mills NL. Nonoperative closure of atrial septal defects. Surgery 1974;75:383e8.
[15] Bridges ND, Hellenbrand W, Latson L, Filiano J, Newburger JW, Lock JE. Transcatheter closure of patent foramen ovale after presumed par-
adoxical embolism. Circulation 1992;86:1902e8.
[16] Meissner I, Whisnant JP, Khandheria BK, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography
and carotid ultrasonography: the SPARC study. Stroke Prevention: assessment of Risk in a Community. Mayo Clin Proc 1999;74:862e9.
[17] Katsanos AH, Giannopoulos S, Frogoudaki A, et al. The diagnostic yield of transesophageal echocardiography in patients with cryptogenic
cerebral ischaemia: a meta-analysis. Eur J Neurol 2016;23:569e79.
[18] Wahl A, Juni P, Mono ML, et al. Long-term propensity score-matched comparison of percutaneous closure of patent foramen ovale with med-
ical treatment after paradoxical embolism. Circulation 2012;125:803e12.
[19] Schuchlenz HW, Weihs W, Berghold A, Lechner A, Schmidt R. Secondary prevention after cryptogenic cerebrovascular events in patients
with patent foramen ovale. Int J Cardiol 2005;101:77e82.
[20] Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012;366:
991e9.
[21] Hornung M, Bertog SC, Franke J, et al. Long-term results of a randomized trial comparing three different devices for percutaneous closure of
a patent foramen ovale. Eur Heart J 2013;34:3362e9.
[22] Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013;368:
1092e100.
[23] Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial.
JAMA 2014;312:1988e98.
[24] Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or Anticoagulation vs. Antiplatelets after stroke. N Engl J Med 2017;377:
1011e21.
[25] Sondergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017;
377:1033e42.
[26] Lee PH, Song JK, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol 2018;71:
2335e42.
[27] Qiu B, Cai Y, Wang D, Lin J, Fan Y. Closure versus medical therapy for patent foramen ovale in patients with cryptogenic stroke: an updated
meta-analysis of randomized controlled trials. J Stroke Cerebrovasc Dis 2018;27(12):3463e72.
[28] Luc JGY, Bakar SN, Kiaii B, Sridhar K. Thrombus in a hypercoagulable patient following patent foramen ovale closure with the gore septal
occluder. JACC Cardiovasc Interv 2018;11:1108e9.
[29] Kodankandath TV, Mishra S, Libman RB, Wright P. Recurrent stroke due to patent foramen ovale closure device thrombus eight years after
implantation. J Stroke Cerebrovasc Dis 2016;25:e161e2.
[30] Ciurus T, Piestrzeniewicz K, Maciejewski M, Luczak K, Jakubowski P, Drozdz J. Thrombus formation on the Amplatzer device: a need for
critical attitude in percutaneous patent ovale closure decision-making. Eur Heart J 2015;36:1195.
[31] Zaman MO, Patel NK, Mojadidi MK. Patent foramen ovale closure for patients excluded from the randomized cryptogenic stroke trials. Clin
Res Cardiol. 2018;107:1187e8.
[32] Meier B, Nietlisbach F. Device closure of the patent foramen, the longer you look, the more you like it. J Am Coll Cardiol. 2019;73:288e90.
[33] Mojadidi MK, Mahmoud AN, Patel NK, Elgendy IY, Meier B. Cryptogenic stroke and patent foramen ovale: ready for prime time? J Am Coll
Cardiol. 2018;72:1183e5.
[34] Brott TG, Howard G, Roubin GS, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med 2016;374:
1021e31.
[35] Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008;358:
1572e9.
[36] Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;
372:1009e18.
[37] Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:
2285e95.
[38] Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;
372:1019e30.
[39] Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:
2296e306.
[40] Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:
11e20.
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
17. PFO CLOSURE: HISTORY, FINAL THOUGHTS, AND FUTURE OUTLOOK220
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CHAPTER
18
The Full Spectrum of PFO: Are We Seeing Just
the Tip of the Iceberg?
M. Khalid Mojadidi
1
, Islam Y. Elgendy
2
, Jonathan M. Tobis
3
, Bernhard Meier
4
1
Virginia Commonwealth University, Richmond, VA, United States;
2
Massachusetts General Hospital and Harvard
Medical School, Boston, MA, United States;
3
University of California, Los Angeles, Los Angeles, CA, United States;
4
University Hospital Bern, Bern, Switzerland
OUTLINE
Clinical Case 221
The Full Spectrum of PFO 222
References
224
CLINICAL CASE
A 41-year-old man was referred for consideration of percutaneous closure of his patent foramen ovale (PFO). The
patient had a recent stroke with temporary expressive aphasia and right hand numbness. Magnetic resonance im-
aging (MRI) confirmed a left-sided parietal stroke, and there was no carotid dissection or atherosclerosis. Although
PFO closure was planned in 2017 due to a high RoPE score of 8 (84% chance that stroke was from the PFO, 6% risk of
2-year stroke recurrence), the insurance company denied it despite multiple appeals. A subsequent event monitor
showed that with peak exertion of riding his bicycle, he developed transient atrial fibrillation. Given his young
age and absence of other comorbidities, it was deemed unlikely that the transient atrial fibrillation could have caused
a thrombus in the left atrial appendage resulting in stroke; paradoxical embolism continued to be the predominant
suspected culprit of stroke. In support of this, an MRI venogram revealed proximal and distal compression of his left
iliac vein by the left common iliac artery, consistent with May-Thurner syndrome. There was no evidence for deep
venous thrombosis and no clinical leg swelling; thus, the left iliac vein was not stented. He was prescribed apixaban
5 mg twice daily.
One year after his initial stroke, the patient presented with nystagmus and dysconjugate gaze; he had a second
stroke involving the basilar artery with MRI- confirmed infarction of the pons territory. Diagnosed too late, he
was not treated with lytic therapy, but his symptoms fortunately resolved. The recurrent stroke occurred with
full medical compliance on apixaban therapy. His neurologist recommended PFO closure. By that time, based on
updated recommendations from the Food and Drug Administration of the United States, the insurance companies
had altered their reimbursement guidelines and authorized payment for a percutaneous PFO closure procedure.
Paroxysmal atrial fibrillation, again, seemed an unlikely culprit because he was on oral anticoagulation at the
time of the recurrent stroke. His cardiologist concluded that apixaban was not completely effective against a poten-
tial venous thrombus that likely passed through the PFO and resulted in paradoxical embolism. Finally, the question
remained whether the left iliac vein compression was the source of venous thrombosis, despite a clinically and prob-
ably insignificant May-Thurner syndrome with absence of proven deep vein thrombosis. The patient was referred
221
PFO Closure for Stroke, Myocardial Infarction, Peripheral Embolism, Migraine, and Hypoxemia
Copyright © 2020 Elsevier Inc. All rights reserved.https://doi.org/10.1016/B978-0-12-816966-7.00018-X
https://t.me/med1917
for atrial fibrillation ablation, followed by percutaneous PFO closure during which a left femoral venogram was
recommended.
THE FULL SPECTRUM OF PFO [1]
A PFO is present in about 25% of the population [2]. Once regarded as a benign anatomical variation, right-to-left
shunting across a PFO has now been recognized to be associated with a wide range of pathologies and clinical syn-
dromes. From paradoxical embolism engendering death, stroke, myocardial infarction, and peripheral ischemia, to
its role in chronic and debilitating conditions such as migraine headache with aura and hypoxemia [3e6], the PFO
maintains its uniqueness among congenital heart defects by choosing to remain clinically silent until it causes
serious trouble.
The ease and safety profile place percutaneous PFO closure among the most practicable interventional cardiology
procedures, with robust long-term clinical yield. Yet, after its introduction in 1992, PFO closure was met with little
enthusiasm and largely ignored for more than 2 decades [7]. The early randomized trials of PFO closure for stroke
fell short of statistical significance, in part due to low-risk patient selection, limited follow-up, and the shortcomings
of intention-to-treat analyses (Chapter 6) [8e10]. Subsequent meta-analyses of these trials, which showed greater effi-
cacy and excellent safety of PFO closure over medical therapy for prevention of recurrent stroke, did little to impress
the skeptics and change respective stroke guidelines [11]. They continued to advise against PFO closure although it had
long been proven at least noninferior and deserved to be offered as an attractive alternative to lifelong blood thinners.
The long-term follow-up of the largest randomized trial [12] was the first to show a statistically significant reduction of
recurrent stroke events, even in the intention-to-treat cohort. It is puzzling that a P-value that had just descended from
formerly .08 in the first publication [10] to .046 [12] suddenly caught everyone’s attention. The positive effect of PFO
closure was achieved despite the presence of 3 patients randomized to the closure arm who had recurrent stroke,
counted as stroke after PFO closure, although they did not actually receive a device. Recently, 3 additional randomized
trials [13e15] and their meta-analyses [16e18] have unequivocally established PFO closure’s superiority over standard
of care blood thinners for secondary prevention of stroke, in patients with a PFO-associated stroke (Chapter 7).
These trials have also expanded our understanding of stroke patients with high-risk PFOs; randomized and non-
randomized studies have shown an even higher clinical yield when PFO closure was performed for patients with
high-risk echocardiographic features (atrial septal aneurysm, septal hypermobility, Eustachian valve, Chiari network,
or major shunt through a large PFO). As an example, the number needed to treat (NNT) in the RESPECT (Randomized
Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment) trial, to
prevent 1 stroke at a 5-year follow-up, was estimated to be 42 [12]; in comparison, a subanalysis of the final RESPECT
trial results (median follow-up 5.9 years) showed a very low NNT when PFO closure was performed for stroke patients
with an atrial septal aneurysm (NNT ¼ 16) or large shunt (NNT ¼ 20) (P-interaction ¼ .04 for both) [12].The
DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk PFO) and
CLOSE (PFO Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence) trials, studies
that only included patients with high-risk PFOs, remarkably demonstrated zero recurrent strokes in the device arm
at 2 and 5 years respectively (NNT ¼ 10 and 20, respectively) [13,15]. Such a therapeutic achievement has yet to be
observed even with the strongest anticoagulant, not to mention the 2%e4% annual risk of bleeding associated with
oral anticoagulation that increases with age. From a pathophysiologic standpoint, it makes sense that high-risk
PFOs are more dangerous. A large PFO exhibits more right-to-left shunting, an atrial septal aneurysm opens the
PFO with virtually every heartbeat, and a Eustachian valve or Chiari network guide thrombi from the inferior vena
cava straight to the PFO opening. A positive result in the randomized trials, even in the presence of some residual
right-to-left shunting post-PFO closure, suggests that the device may act as a filter even when the PFO is not completely
sealed [12,14]. It is hypothesized that this may not be the case with suture closure of a PFO. Now that the characteristics
have been identified that make a PFO dangerous, is there a role of PFO closure for primary prevention in those patients,
particularly if they are also at high risk for venous thromboembolism? Screening and investigating patients who are
undergoing major surgery [19] or those with deep venous thrombosis or pulmonary embolism [20,21] would be a
good place to start looking.
The prevalence of paradoxical embolism from a PFO is underestimated in clinical medicine. Other identified
causes are usually blamed first, such as ruptured atherosclerotic plaque, spontaneous cerebral or coronary dissec-
tions, or atrial fibrillation. The PFO may be the first culprit identified, but it is the last one blamed. This is as illogical
as the following analogy. The police are informed about a burglary in the village. They ignore the burglar called PFO
sitting right in front of the police station but rather swarm out to painstakingly round up all other notorious local
18. THE FULL SPECTRUM OF PFO: ARE WE SEEING JUST THE TIP OF THE ICEBERG?222
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
https://t.me/med1917
burglars and check their alibis. They are all clean. Only then, the police take in the easiest to apprehend burglar
called PFO. Perhaps this is because it is common to in cidentally find a PFO in adults, but is that not equally the
case for atrial fibrillation in the elderly [22]? We do not hesitate to place atrial fibrillation patients on oral anticoagu-
lation, despite the annual bleeding risk of anticoagulants and knowing that some atrial fibrillation patients may
never have a stroke without anticoagulation. Despite a better efficacy and safety profile than oral anticoagulants,
and absent concern for compliance of taking a pill a day, PFO device closure is used as a last resort only if no other
stroke causes exist. Is it because PFO closure is a remunerated procedure done by cardiologists rather than a pill a
day prescribed by any doctor? The notion that a PFO cannot cause a stroke in the presence of anoth er cause of stroke
is counterintuitive; no medical condition is treated this way. For example, if an ischemic stroke patient presents with
both atrial fibrillation and carotid disease, do we treat the carotid stenosis and ignore the atrial arrhythmia? The inac-
curate assumption that the PFO is the culprit only in the absence of other culprits makes paradoxical embolism an
underestimated and underdiagnosed entity in real life. Furthermore, considering that the coronary to cerebral blood
flow ratio is 1:3 (220 vs. 750 mL/min), 1 right-to-left shunt-mediated myocardial infarction per 3 right-to-left
shunt-mediated cerebral ischemic events makes more sense than the estimated 1:100,000 incidence reported in
the literature. One large 20-year cohort study found a high rate of coincidental strokes and myocardial infarctions
among patients presenting with acute pulmonary embolism [23]. Despite the fact that the literature had already
established PFO as a culprit for simultaneous embolisms in the systemic and pulmonary circulations [20], PFO
was inexcusably not mentioned in the paper [23] or the accompanying editorial [24]. More recently, this has been
rectified as the literature continues to prove a higher incidence of ischemic strokes in symptomatic pulmonary em-
bolism patients who have a PFO, when compared to those with no PFO [22,25].
Based on a large autopsy study, the prevalence of PFO decreases from 34% during the first 3 decades of life to
25% during the fourth to eighth decade, and then 20% thereafter [2]. This observation must be accounted for by
either spontaneous PFO closure later in life or selective mortality (lower life expectancy of PFO carriers). However,
there have been no reports of transesophageal echocardiographyedocumented spontaneous closure of a PFO over
time. Most people with a PFO will remain asymptomatic for life. Yet, since the early initial report of a young woman
who died of a PFO-mediated stroke by Julius Cohnheim in 1877 [26], the potential of the PFO pathway to kill has
been apparent and was corroborated when comparing mortality in PFO carriers with and without device closure
FIGURE 18.1 Established indication (visible tip of the iceberg) and plausible indications (invisible body of the iceberg) for device closure of the
PFO. Adapted with permission from Ref. [1].
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
THE FULL SPECTRUM OF PFO 223
https://t.me/med1917
[27]. Our understanding of PFOs and high-risk PFOs has increased over time, along with improved technique, ease,
and safety of device closure. Percutaneous PFO closure is now accomplished easily as a same-day procedure with
minimal discomfort and risk. Patients can go back to their usual routine the same day, and posttreatment usually
consists of a few months of low-dose acetylsalicylic acid. Postclosure atrial fibrillation/flutter occurs in about 5%
of procedures [16e18]; however, these arrhythmias are usually early, transient, and they rarely cause stroke or
need any, let alone long-term, anticoagulation. Of all patients randomized to a device in the cryptogenic stroke trials,
0.1% had recurrent stroke presumed to be from device-associated atrial fibrillation [28,29]. The 4 statistically positive
PFO closure trials showed a NNT of 10e42 to prevent 1 stroke in 2e5 years [12e14]; it has been previously extrap-
olated that the NNT may be as low as just 2 PFOs closed to prevent 1 stroke with a lifelong follow-up [30]. With a cost
generously estimated at $10,000e$20,000, procedural simplicity, excellent efficacy and safety, PFO closure for stroke
seems like a no-brainer (pun intended).
Paradoxical embolism causing stroke, myocardial infarction, or peripheral embolism is only part of the story. PFO
closure reduces the frequency and duration of migraine with aura [4,5]; can make it safer to live or climb in high
altitude [31], dive [32,33], undergo major surgery [19]; and improves hypoxemia from sleep apnea [34,35],
platypnea-orthodeoxia [36], and exercise desaturation [6,37]. Moreover, PFO closure for one indication provides a
collateral benefit for the other indications, all at the same cost. A migraineur treated with PFO closure gets lifelong
protection from paradoxical embolism and PFO-mediated hypoxemia, and vice versa. Despite a multitude of obser-
vational studies on PFO closure, 9 completed randomized trials, and more ongoing trials, we are seeing just the tip of
the iceberg (Fig. 18.1) [1]. With this in mind, it is time to stop calling it an “innocent bystander” and reclassify the PFO
for what it really is: the most common congenital defect in the world, with a license to kill [1].
References
[1] Meier B, Nietlispach F. The evil of the patent foramen ovale: we are seeing but the tip of the iceberg. Eur Heart J 2018;39:1650e2.
[2] Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965
normal hearts. Mayo Clin Proc 1984;59:17e20.
[3] Mojadidi MK, Zaman MO, Elgendy IY, et al. Cryptogenic stroke and patent foramen ovale. J Am Coll Cardiol 2018;71:1035e43.
[4] Mattle HP, Evers S, Hildick-Smith D, et al. Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial.
Eur Heart J 2016;37:2029e36.
[5] Tobis JM, Charles A, Silberstein SD, et al. Percutaneous closure of patent foramen ovale in patients with migraine: the PREMIUM trial. J Am
Coll Cardiol 2017;70:2766e74.
[6] Mojadidi MK, Ruiz JC, Chertoff J, et al. Patent foramen ovale and hypoxemia. Cardiol Rev 2019;27:34e40. https://doi.org/10.1097/
CRD.0000000000000205.
[7] Bridges ND, Hellenbrand W, Latson L, Filiano J, Newburger JW, Lock JE. Transcatheter closure of patent foramen ovale after presumed par-
adoxical embolism. Circulation 1992;86:1902e8.
[8] Furlan AJ, Reisman M, Massaro J, et al. CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen
ovale. N Engl J Med 2012;366:991e9.
[9] Meier B, Kalesan B, Mattle HP, et al. PC Trial Investigators. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J
Med 2013;368:1083e91.
[10] Carroll JD, Saver SL, Thaler DE, et al. RESPECT Investigators. Closure of patent foramen ovale versus medical therapy after cryptogenic
stroke. N Engl J Med 2013;368:1092e100.
[11] Kent DM, Dahabreh IJ, Ruthazer R, et al. Device closure of patent foramen ovale after stroke: pooled analysis of completed randomized trials.
J Am Coll Cardiol 2016;67:907e17.
[12] Saver JL, Carroll JD, Thaler DE, et al. RESPECT Investigators. Long-term outcomes of patent foramen ovale closure or medical therapy after
stroke. N Engl J Med 2017;377:1022e32.
[13] Mas JL, Derumeaux G, Guillon B, et al. CLOSE Investigators. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke.
N Engl J Med 2017;377:1011e21.
[14] Søndergaard L, Kasner SE, Rhodes JF, et al. Gore REDUCE Clinical Study Investigators. Patent foramen ovale closure or antiplatelet therapy
for cryptogenic stroke. N Engl J Med 2017;377:1033e42.
[15] Lee PH, Song J-K, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol 2018;71:
2335e42.
[16] Mojadidi MK, Elgendy AY, Elgendy IY, et al. Transcatheterpatent foramen ovale closure after cryptogenic stroke: an updated meta-analysis of
randomized trials. J Am Coll Cardiol Intv 2017;10:2228e30.
[17] Shah R, Nayyar M, Jovin IS, et al. Device closure versus medical therapy alone for patent foramen ovale in patients with cryptogenic stroke: a
systematic review and meta-analysis. Ann Intern Med 2018;168:335e42.
[18] De Rosa S, Sievert H, Sabatino J, Polimeni A, Sorrentino S, Indolfi C. Percutaneous closure versus medical treatment in stroke patients with
patent foramen ovale: a systematic review and meta-analysis. Ann Intern Med 2018;168:343e50.
[19] Ng PY, Ng AK, Subramaniam B, et al. Association of preoperatively diagnosed patent foramen ovale with perioperative ischemic stroke. J Am
Med Assoc 2018;319:452e62.
[20] Konstantinides S, Geibel A, Kasper W, Olschewski M, Blu
¨
mel L, Just H. Patent foramen ovale is an important predictor of adverse outcome in
patients with major pulmonary embolism. Circulation 1998;97:1946e51.
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
18. THE FULL SPECTRUM OF PFO: ARE WE SEEING JUST THE TIP OF THE ICEBERG?224
https://t.me/med1917
[21] Le Moigne E, Timsit S, Ben Salem D, et al. Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective
Cohort Study. Ann Intern Med 2019. https://doi.org/10.7326/M18-3485 [Epub ahead of print].
[22] Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: european perspective. Clin Epidemiol 2014;6:213e20.
[23] Sørensen HT, Horvath-Puho E, Pedersen L, Baron JA, Prandoni P. Venous thromboembolism and subsequent hospitalisation due to acute
arterial cardiovascular events: a 20-year cohort study. Lancet 2007;370:1773e9.
[24] Lowe GD. Is venous thrombosis a risk factor for arterial thrombosis? Lancet 2007;370:1742e4.
[25] Schmidt MR, Søndergaard L. Patent Foramen Ovale: A Villain in Pulmonary Embolism? Ann Intern Med 2019. https://doi.org/10.7326/
M19-1089 [Epub ahead of print].
[26] Cohnheim J. Vorlesungen uber allgemeine Pathologie-ein Handbuch Fur Aerzte und Studirende. Erste Ausgabe 1877. Berlin, Hirschwald.
[27] Wahl A, Juni P, Mono ML, et al. Long-term propensity score-matched comparison of percutaneous closure of patent foramen ovale with med-
ical treatment after paradoxical embolism. Circulation 2012;125:803e12.
[28] Mojadidi MK, Elgendy AY, Elgendy IY, Mahmoud AN, Meier B. Atrial fibrillation after percutaneous patent foramen ovale closure. Am J
Cardiol 2018;122:915. https://doi.org/10.1016/j.amjcard.2018.05.035.
[29] Elgendy AY, Elgendy IY, Mojadidi MK, Mahmoud AN, Barry JS, Jneid H, Wayangankar SA, Tobis JM. B. Meier. New-onset atrial fibrillation
following percutaneous patent foramen ovale closure: a systematic review and meta-analysis of randomised trials. EuroIntervention 2019;14:
788e1790.
[30] Meier B, Nietlispach F. Editorial Commentary: closure of the patent foramen ovale viewed from a different angle. Trends Cardiovasc Med
2017;27:582e4.
[31] Allemann Y, Hutter D, Lipp E, et al. Patent foramen ovale and high-altitude pulmonary edema. J Am Med Assoc 2006;296:2954e8.
[32] Billinger M, Zbinden R, Mordasini R, et al. Patent foramen ovale closure in recreational divers: effect on decompression illness and ischaemic
brain lesions during long-term follow-up. Heart 2011;97:1932e7.
[33] Mojadidi MK, Christia P, Salamon J, et al. Patent foramen ovale: unanswered questions. Eur J Intern Med 2015;26:743e51.
[34] Agnoletti G, Iserin L, Lafont A, Sidi D, Desnos M. Obstructive sleep apnea and patent foramen ovale: successful treatment of symptoms by
percutaneous foramen ovale closure. J Interv Cardiol 2005;18:393e5.
[35] Mojadidi MK, Bokhoor PI, Gevorgyan R, et al. Sleep apnea in patients with and without a right-to-left shunt. J Clin Sleep Med 2015;11:
1299e304.
[36] Mojadidi MK, Gevorgyan R, Noureddin N, Tobis JM. The effect of patent foramen ovale closure in patients with platypnea-orthodeoxia
syndrome. Cathet Cardiovasc Interv 2015;86:701e7.
[37] Devendra GP, Rane AA, Krasuski RA. Provoked exercise desaturation in patent foramen ovale & impact of percutaneous closure. J Am Coll
Cardiol Intv 2012;5:416e9.
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
REFERENCES 225
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CHAPTER
19
Frequently Asked Questions: PFO Closure
With the Amplatzer or Gore Cardioform
Devices
Jonathan M. Tobis
1
, M. Khalid Mojadidi
2
, Bernhard Meier
3
1
University of California, Los Angeles, Los Angeles, CA, United States;
2
Virginia Commonwealth University, Richmond,
VA, United States;
3
University Hospital Bern, Bern, Switzerland
OUTLINE
Introduction 228
Percutaneous Closure of Interatrial Shunts:
PFO or Atrial Septal Defect 228
What Is a PFO? 228
What Is a Cryptogenic Stroke? 228
Estimate of Incidence of Cryptogenic Stroke
Due to PFO 229
How Does a PFO Cause a Stroke? 229
What Alternative Treatments Are Available? 229
Randomized Controlled Clinical Trials of PFO
Closure for Stroke: The RESPECT, REDUCE,
CLOSE, and DEFENSE-PFO Trials 230
An Explanation of the Procedure to Close a PFO
With the Amplatzer or Gore Cardioform Device 230
PFO Closure for Migraine Headaches 230
What Possible Complications Can Occur? 231
What Side Effects Can Occur With the PFO Closure
Device? 231
What Instructions Must I Follow After I Have a PFO
Closure Device Placed? 232
Could My PFO Have Contributed to My Transient
Ischemic Attack?
232
Why Was My PFO Not Previously Detected? Is
Echocardiography the Only Way to Diagnose
This?
232
I Had a Transient Ischemic Attack; Are There Any
Other Tests You Would Recommend for Me?
232
How Soon Should I Have This Procedure?
232
What Is the Recovery Like?
232
Is There Any Exclusion Criteria to Device Closure?
233
Will I Be Able to Feel the Device?
233
Can I Travel With the Implanted Device? Will the
Device Trigger Airport Security Systems?
233
Can I Have a Magnetic Resonance Imaging Study
After Having the Device Implanted?
233
Can I Have My PFO Closed if I Am Pregnant?
233
In Your Expert Opinion, Is There Anything Else I
Should Know or Consider Prior to Having My
PFO Closed?
233
227
PFO Closure for Stroke, Myocardial Infarction, Peripheral Embolism, Migraine, and Hypoxemia
Copyright © 2020 Elsevier Inc. All rights reserved.https://doi.org/10.1016/B978-0-12-816966-7.00019-1
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INTRODUCTION
A 30-year-old woman had a stroke 3 months ago and is now referred to you after being evaluated by a
neurologist. There is no obvious source of the stroke, but a patent foramen ovale (PFO) was identified by transeso-
phageal echocardiography (TEE) with right-to-left shunting. Your new patient has a lot of questions and you do not
have a lot of time. We have written this chapter based on frequent questions that we have received over the years.
You may choose to print this out and give to your patient, or adapt it to your practice.
PERCUTANEOUS CLOSURE OF INTERATRIAL SHUNTS: PFO OR ATRIAL SEPTAL
DEFECT
In the past, the only way to close a hole in the heart that produced an abnormal connection between 2 chambers
was to perform open-heart surgery. For over 25 years, catheter-based devices have been available as an alternative to
open-heart surgery, and some devices have been approved by the Food and Drug Administration (FDA) since 2001.
They permit us to close abnormal connections (shunts) between the right and left atrium (an atrial septal defect or
ASD) without needing open-heart surgery. This technique is performed in the cardiac catheterization laboratory by
an interventional cardiologist. During this procedure, a small tube called a catheter is placed in the heart from the
large vein in the groin. A special spring-loaded device is passed through the catheter and straddles the hole between
the 2 heart chambers. The procedure takes less than an hour and is performed without the necessity for general anes-
thesia. The patient can usually go home the same day. Imaging with X-ray fluoroscopy or echocardiography are used
to guide the atrial septal defect procedure according to the operator’s choice.
What Is a PFO?
The foramen ovale is a small passageway in the heart that all people have at birth. The foramen ovale permits
oxygen-rich blood to pass from the placenta in the mother’s womb to the left side of the baby’s heart. From there,
this blood can travel to the vital organs in the baby’s body. Once the baby is born, the lungs expand with air, and the
pressures inside the heart change. This forces a flap to close over the PFO passageway. After a few months, this flap
normally seals over with scar tissue which prevents any further blood from mixing between the left and right sides
of the heart.
However, in over 20% of people, the foramen ovale passageway does not seal over and it remains patent (able to
open). In the vast majority of people, this does not cause any problem. However, in adulthood small blood clots form in
the veins of the lower body in all people. They are usually harmless because of their small size, even if they travel to the
lung. A large blood clot is dangerous and can cause a pulmonary embolus, but we are talking about clots that are usu-
ally 1e3 mm in size. If there is a PFO, however, the blood clot may cross over and reach important and delicate organs
such as the brain, the eye, or the coronary arteries supplying the heart. Even very small blood clots may cause damage
there. Some people, for instance, develop a stroke that cannot be explained by the usual causes. This is called a cryp-
togenic (unknown cause) stroke. It has been observed that a high percent of people (60%e70%) with a stroke of unknown
cause, have a PFO. Hence, such a crossover of a blood clot (paradoxical embolism) is assumed as the reason for their
stroke.
What Is a Cryptogenic Stroke?
“Cryptogenic” means of unknown cause. A stroke or a transient ischemic attack (TIAda neurologic deficit that
resolves completely within a day) is usual ly caused by one of the following: (1) hardening or fissure of the arteries
that lead to the brain, (2) a blood clot from the heart or the aorta that lodges in the brain, or (3) an abnormality of the
arteries in the brain. All of these conditions block the blood flow to a region of the brain and impair its function. If the
patient does not have any of these problems or any other known cause for the stroke (there are many), then the stroke
is said to be “cryptogenic.”
There is a high association of people with cryptogenic stroke and a PFO. This is especially true in younger people,
20e60 years old, who usually are not at a high risk of having a stroke due to hardening of the arteries. The recurrence
rate in people who have a cryptogenic stroke and a PFO is about 1% per year, but this ri sk appears to be constant and
additive, so the longest study showed a 10% recurrent stroke risk over 10 years.
19. FREQUENTLY ASKED QUESTIONS: PFO CLOSURE WITH THE AMPLATZER OR GORE CARDIOFORM DEVICES228
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
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Estimate of Incidence of Cryptogenic Stroke Due to PFO
There are 700,000 strokes/year in the United States; 100,000 of these are cryptogenic. The prevalence of PFO
among cryptogenic stroke patients is estimated to be between 60% and 70%. The refore 60,000e70,000 strokes/
year in the United States are potentially caused by paradoxical embolism through a PFO. From an individual’s
perspective, if 20% of all people have a PFO, then there are approximately 65 million people in the United States
who have a PFO and do not know about it. If we estimate that there are 60,000 cryptogenic strokes per year due
to a PFO, then the risk to develop a stroke for a person with a PFO is 1 in 1000 people per year. This risk may be
higher if the PFO is opening up very often, is big, or has a large amount of blood crossing it.
How Does a PFO Cause a Stroke?
Our current theory is that a small blood clot may form in the veins of the leg and pass from the veins into the right
atrium of the heart. Normally a small blood clot in the right side of the heart will travel to the lungs and be trapped
and not cause any notice. A very large blood clot can plug up a large artery in the lungs and cause significant prob-
lems. This is termed pulmonary embolism. However, blood clots that pass through a PFO are usually much smaller,
about 1e3 mm in diameter. If a person happens to have a PFO and also happens to develop a blood clot in the veins,
there is a small chance that the blood clot could travel from the vein to the right side of the heart, through the PFO,
into the left side of the heart, and from there it could go to the brain and cause a stroke or to another sensitive organ.
Although the chance of this is small, the possibility of this coincidence increases as you get older and perhaps
develop other illnesses that promote blood clots, like varicose veins. On average, approximately 1 in 1000 peo-
ple/year with a PFO may develop a stroke. The risk is dependent on the characteristics of the PFO and does not
include damage to other organs, such as the heart and the eye.
Although it is difficult to prove that the PFO is the intermediary passageway for a blood clot to cause a stroke,
there are some lines of evidence that suggest this may be the case:
1) Although a PFO is found in 20% of the population, a PFO is found in 60%e70% of people who have a crypto genic
stroke.
2) If the PFO is closed, the chance of developing a subsequent recurrent stroke is reduced dramatically (about 75%).
What Alternative Treatments Are Available?
If someone has a cryptogenic stroke, and a PFO is documented by TEE (a form of imaging the heart where the
ultrasound probe is placed in the esophagus through the mouth), there are currently 3 ways of trying to prevent
another stroke.
1) The patient can be placed on a potent blood thinner called warfarin (Coumadin, the traditional blood thinner),
apixaban, dabigatran, edoxaban, or rivaroxaban. Blood thinners have been used for over 50 years and are given to
patients who have atrial fibrillation, a common arrhythmia especially in elderly people causing strokes from
blood clots that form in an upper heart chamber, or prosthetic heart val ves to prevent blood clots from forming on
the foreign substance. Although these blood thinners can be used safely, they harbor a definite risk of internal
bleeding. This is especially bothersome for our active patients who participate in athletic activities. Weaker blood
thinners, such as acetylsalicylic acid and clopidogrel, have also been used because they cause less bleeding, but
their protection is suboptimal.
2) The PFO can be closed surgically. This requires open-heart surgery where the circulation is maintained by passing
the blood through a heartelung bypass machine. In addition to the obvious trauma of the operation and the
required recuperation, there is much concern that the bypass machine causes small particles to go to the brain.
Some patients report subtle memory or personality changes following open-heart surgery and we suspect this
may be due to the bypass machine. Such surgery is rarely performed as an isolated interven tion anymore.
3) In October 2016, the FDA approved the use of the Amplatzer PFO Occluder (Abbott, Chicago, Illinois) device for
PFO closure, and in March 2018, use of the Gore Cardioform Septal Occluder (W.L. Gore and Associates, Flagstaff,
Arizona). Outside of the United States, these and similar devices have been available for over 25 years. Placing
these devices is a lot easier on the patient than having open-heart surgery. The procedure is don e in the cardiac
catheterization laboratory using X-ray imaging and often some form of echocardiography to guide the catheter
that is used to place the device. The procedure is relatively simple, takes less than an hour to perform, and does
not require hospitalization.
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
PERCUTANEOUS CLOSURE OF INTERATRIAL SHUNTS: PFO OR ATRIAL SEPTAL DEFECT 229
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RANDOMIZED CONTROLLED CLINICAL TRIALS OF PFO CLOSURE FOR STROKE: THE
RESPECT, REDUCE, CLOSE, AND DEFENSE-PFO TRIALS
The best way to determine if a procedure or a drug should be used is to test the new procedure against the current
standard clinical treatment. The RESPECT trial was performed with the Amplatzer PFO Occluder device. The 5-year
results of this trial showed that for patients who had a cryptogenic stroke, the recurrence rate on medical therapy
was 1.7% per year. For the patients who were assigned to the PFO closure group, the risk of recurrent stroke was
reduced by 70%, which was statistically significant.
The REDUCE trial tested the Cardioform Clo sure Device by the W.L. Gore company. It is made from Gore-Tex and
has springs that form 2 discs on the left and right atrial sides of the septum or wall between the 2 upper chambers of
the heart. The REDUCE trial showed a significant reduction in preventing recurrent stroke in people who had a
“cryptogenic stroke.”
The CLOSE trial in Europe demonstrated clinical benefit of PFO closure in people who had a large shunt or an
atrial septal aneurysm (a term used when the thin wall between the upper 2 heart chambers appears pliable and
redundant). None of the patients who had their PFO closed had another stroke during a follow-up of up to 6 years.
In the medically treated groups, the recurrent stroke rate was about 1% per year. No definitive difference could be
proven if coumarin blood thinner was used versus an antiplatelet blood thinner such as acetylsalicylic acid or clo-
pidogrel, but overall coumarin appears more effective.
A fourth randomized clinical trial, the DEFENSE-PFO trial in South Korea, also demonstrated a profound clinical
benefit of PFO closure in people who had similar anatomical variants as in the CLOSE trial. The study included pa-
tients with a large PFO or hypermobile septum or atrial septal aneurysm. Similar to the CLOSE trial, none of the
patients who had their PFO closed had another stroke during a follow-up of 2 years.
An Explanation of the Procedure to Close a PFO With the Amplatzer or Gore Cardioform Device
The patient comes to the hospital on the morning of the procedure and is brought to the cardiac catheterization
laboratory. Some sedation may be given, such as an intravenous tranquilizer or even a morphine-derivative.
Intravenous heparin, a short-acting blood thinner, is given while we are working inside the heart. We numb up
the groin to access the femoral vein with a needle. A tube is placed into the femoral vein, similar to starting a large
IV. An echocardiography probe may also be passed through a vein in the leg into the right atrium to image the heart.
A special long tube called a catheter and a long wire are passed under X-ray guidance into the heart, across the PFO,
and into the left atrium. The device is loaded into a special delivery catheter. The device is placed in the left atrium
and the distal disc is opened. The disc is then pulled snug against the left side of the PFO. When we are convinced
that the device is in the correct position, we unfold the second disc in the right atrium side of the PFO. This encloses
or sandwiches the PFO between the 2 discs of the device. The device is then released from its delivery catheter. The
final position is observed with injecting some contrast medium or with intracardiac echocardiography before the
procedure is finished. Some centers use TEE during the procedure and this requires stronger sedation or even brief
general anesthesia with a respiratory tube. The patient is observed in the monitoring area of the hospital. If there are
no complications, the patient is discharged that evening.
PFO Closure for Migraine Headaches
The frequency of PFO is increased in people who have migraine with aura; about 50% of these people have a PFO
compared to 20% in the general population. Many groups have found that when they close a PFO for indications
such as stroke, the patients who also had migraines often described a reduction in the frequency and severity of their
migraine episodes, and quite a few tell us that the migraines are completely gone. This observation was tested in 2
randomized controlled trials called the PRIMA and the PREMIUM studies. They included patients with very severe
and frequent migraines, between 6 and 14 days of headache per month, in people wh o were unresponsive to mul-
tiple medications. The frequency of migraine days was reduced to a greater extent in people who had their PFO
closed (an average reduction of 3.2 vs. 2.0 days). It was especially effective in people who had migraine with frequent
episodes of aura (greater than 50% of their attacks were with aura).
VII. SAFETY, TECHNICAL ASPECTS TO PFO CLOSURE, AND FUTURE OUTLOOK
19. FREQUENTLY ASKED QUESTIONS: PFO CLOSURE WITH THE AMPLATZER OR GORE CARDIOFORM DEVICES230
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