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TABLE 8.3 Myocardial Infarction in Randomized Secondary Prevention PFO Closure Trials.
Trial Inclusion Criteria
Number of
Patients
Follow-Up
Duration Primary Endpoint Interventional Arm Control Arm
History of Myocardial
Infarction at Baseline
Cardiac Events during
Follow-up (Descriptive,
No Statistically
Significant Findings)
CLOSURE I
[35]
Stroke/TIA due to
presumed paradoxical
embolism
909 2 years Composite of stroke,
TIA, and death
STARFlex septal
closure system plus
medical therapy
(ASS, warfarin, or both)
Medical therapy
alone
12/909 patients (1.3%) 2 (0.5%) deaths due to
cardiac arrhythmia/
arrest in the closure
group
Myocardial infarctions
not reported
PC [33] Cryptogenic stroke,
TIA, or peripheral
thromboembolic event
414 4 years Composite of death,
nonfatal stroke, TIA,
or peripheral embolism
Amplatzer PFO
Occluder
Medical therapy
(antiplatelet or OAC)
4/414 patients (1.0%) Myocardial infarction in
1.0% of patients in the
PFO-closure group and
0.5% in the medical
group
CLOSE [6] Stroke attributed to
PFO with associated
atrial septal aneurysm
or large interatrial shunt
663 5.3 years Stroke PFO closure (several
devices, mostly
Amplatzer PFO
Occluder)
Antiplatelet or OAC
(2 control groups)
1/633 patients (0.2%) 1 acute coronary
syndrome and 2
coronary embolisms in
the PFO-closure group
RESPECT [8] Cryptogenic stroke 980 5.9 years Composite of nonfatal
stroke, fatal stroke, or
early death after
randomization (45 days)
Amplatzer PFO
Occluder plus 1 month
double antiplatelet
therapy and 5 months
acetylsalicylic acid
Medical therapy
(antiplatelet or OAC)
7/980 patients (0.7%);
recent (<6 months)
myocardial infarction
was exclusion criterion
4 cardiac arrests (1
PFO-C, 3 MT); 9
myocardial infarctions
(7 PFO-C, 2 MT); 8
patients with other
symptomatic coronary
artery disease (5 PFO-
C, 3 MT)
Gore
REDUCE [7]
Cryptogenic stroke 664 3.2 years Coprimary endpoints:
(1) freedom from ischemic
stroke (clinically evident);
(2) incidence of new brain
infarction (clinical or
subclinical)
Helex Septal Occluder
or Cardioform Septal
Occluder plus
antiplatelet therapy
Antiplatelet therapy Prior myocardial
infarction was
exclusion criterion
1 cardiac arrest in the
medical group
DEFENSE-PFO
[34]
Cryptogenic stroke
and high-risk PFO
120 2.8 years Composite of stroke,
vascular death or
TIMI-bleeding during
2 years of follow-up
Amplatzer PFO
Occluder
Medical therapy
(antiplatelet or OAC)
History of myocardial
infarction or unstable
angina were exclusion
criteria
No systemic embolism
occurred; no myocardial
infarction reported
CLOSE, PFO Closure or Anticoagulants versus Antiplatelet Therapy to Prevent Stroke Recurrence; CLOSURE I, Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed
Paradoxical Embolism through a PFO; DEFENSE-PFO, Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk PFO; Gore REDUCE, Gore Helex Septal Occluder/Gore Cardioform Septal Occluder and
Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed Transient Ischemic Attack in Patients with PFO; MT, medical therapy; OAC, oral anticoagulation; PC, Percutaneous Closure of PFO in Cryptogenic
Embolism; PFO-C, PFO closure; RESPECT, Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment; TIA, transient ischemic attack.
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would be the most likely explanation for the simultaneous occurrence of stroke or MI with a DVT or pulmonary em-
bolism [25].
DIFFERENTIAL DIAGNOSIS
Suspicion of a PFO-mediated MI is understandably highest in young patients who present with an MI without
traditional cardiovascular risk factors and with otherwise normal coronary arteries. Nevertheless, the presence of
atherosclerosis or atrial fibrillation does not exclude the possibility of a paradoxical embolic cause, especially when
predisposing factors are present. Predisposing factors for paradoxical coronary embolism are the same as those for
paradoxical embolic stroke (Table 8.2). Prothrombotic states increase the probability for a venous thrombosis as a
source for paradoxical embolism (Fig. 8.2). Concomitant pulmonary embolism associated with any ischemic event
(stroke, myocardial, renal, mesenteric, or peripheral limb infarction) is very suggestive of a paradoxical embolic cause.
Coronary embolism may be difficult to distinguish from several other causes of MI. The most important differential
diagnosis is spontaneous coronary artery dissection (SCAD). SCAD is categorized into 3 angiographic types: type 1
with contrast staining the false lumen, type 2 as a smooth diffuse stenosis, and type 3 with features similar to athero-
sclerosis [38,39]. Angiographically, SCAD may be indistinguishable from a coronary embolus (whether paradoxical or
(A)
(B)
(C)
(D)
(E)
FIGURE 8.2 PFO and myocardial infarction (MI) in a young woman with risk factors for thromboembolism. A31-year-oldwomanpresented
to the emergency room with ongoing chest pain, which had started 2 hours earlier while smoking. Electrocardiogram showed inferior ST-segment
elevation and ST-segment depression in leads V1-3 (A) The patient was brought to the cardiac catheterization laboratory. Coronary angiography of
the right coronary artery revealed an embolic-looking occlusion of the posterolateral branch (B, arrow) with otherwise normal coronary arteries. The
occlusion was treated with thrombus aspiration. Due to the high suspicion of paradoxical coronary embolism in the presence of several risk factors
for venous thromboembolism (smoking status, overweight, oral contraceptives), a PFO was searched for, found, and closed with a 25 mm Amplatzer
PFO Occluder during the same procedure (C D). Circumscribed posterior MI was confirmed later by transmural late gadolinium enhancement with
cardiacmagnetic resonance imaging (E, between arrows).Hematologic examinations revealed antiphospholipid syndrome as an additional risk factor
for venous thromboembolism. Although long-term oral anticoagulation was recommended by the hematologist, it may not really be required after
PFO closure in this young female. PFO closure may prevent recurrent paradoxical embolic events in situations, when anticoagulation must be
interrupted, e.g., during a subsequent pregnancy. LAA, left atrial appendage; SS, septum secundum.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
DIFFERENTIAL DIAGNOSIS 103
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nonparadoxical). The definite diagnosis of SCAD is even difficult with intracoronary imaging to detect intramural he-
matoma or intimal-medial flap [40]. Due to the increased risk of iatrogenic dissection in SCAD patients, intracoronary
imaging is frequently avoided. Another reason to consider paradoxical coronary embolism in patients with presumed
SCAD is the broad overlap of clinical risk factors. (1) SCAD predominantly occurs in women during the peripartum
period, and hormonal changes are considered to contribute to the predisposition for SCAD but equally for paradoxical
embolism through a PFO. Women who take hormonal contraception, are obese, or actively smoke may also be more
prone to SCAD, venous thromboembolism, and paradoxical embolism (Fig. 8.2). (2) SCAD is preceded by extraordi-
nary physical efforts in 28% of cases [41], even more frequently in men. Physical triggers may be associated with a
Valsalva maneuver, which supports the passage of thrombus through a PFO allowing paradoxical arterial embolism.
(3) A substantial proportion of patients in SCAD registries suffer from migraine headache [41]. Migraine with aura is
(A)
(B)
(C)
(D)
FIGURE 8.3 Findings suggesting myocardial infarction (MI) by paradoxical embolism in 2 patients. Angiographic findings of a 49-year-old
woman presenting with cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO, A) during coronary angiography revealing
multiple coronary vessel occlusions (A, arrows). Pulmonary angiography revealed multiple emboli in the right pulmonary artery (B, arrows). The
concomitant finding of (multiple) pulmonary artery and (multiple) coronary artery occlusion(s) all but proves MI by paradoxical embolism.
Angiography of a 46-year-old woman presenting with chest pain 1 week after calf swelling and tenderness showed a long-segment thrombotic
obstruction of the distal right coronary artery (C, between arrows). The thrombus is outlined by a contrast silhouette which is typical for embolic
obstruction. Macroscopically the extracted thrombus appeared partially organized (D), presumably from the indwelling time in the venous
circulation. Deep vein thrombosis of the legs could no longer be documented by Duplex sonography; coronary obstruction by paradoxical em-
bolism is highly suggestive in this obese female without coronary atherosclerosis, albeit it would still be suggestive if there was atherosclerosis.A
PFO was found and closed in the same procedure in both patients.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
8. MYOCARDIAL INFARCTION AND PFO104
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also associated with PFO [37]. (4) SCAD may occur in multiple vessels, either concomitantly or at different times.
Notwithstanding, simultaneous multivessel presentation is an even more compelling feature of paradoxical coronary
embolism with resultant diffuse dissemination of embolic thrombotic material (Fig. 8.3A).
Since thromboembolic material may resolve spontaneously or by thrombolytic medication at the time of
coronary angi ography, coronary embolism should be a differential diagnosis in an MI with angiographically
nondiseased coronary arteries. To consider the m ost important possible etiologies, a consensus paper
recommends a syste matic diagnostic algorithm including the review for subtle missed angiographic fi ndings
(dissection, emboli, plaque disruption), the administration of intrac oronary nitrates (to exclude coronary spasm),
correlation with ventriculography and echocardiography (to exclude Takotsubo or other cardiomyopathies), and
the consideration of intravascular imaging (to exclude plaque rupture/erosion and dissection), or pressure wire
assessment to detect microvascular dysfunction. Furthermore, cardiac m agnetic resonance imaging may help to
differentiate between an ischemic (subendocardial late gadolinium enh ancement) and inflammatory (diffuse or
patchy late gadolinium enhancement) etiology in unclear situations [42].
In the presence of atherosclerotic disease, venous thromboembolism is quite prevalent due to shared risk factors.
The prevalence of both conditions increases with age (Fig. 8.1) [43,44] and is higher in patients who are obese or
diabetic, and who smoke. Consequently, numerically most paradoxically embolic MIs occur in patients with
some degree of coronary atherosclerosis. Only in relative statistics, paradoxical coronary embolism is less probable
in patients with coronary atherosclerosis. However, patients with atherosclerotic coronary stenosis >25% are usually
excluded in studies assessing the frequency of paradoxical embolic MI [11,14]. As a consequence, this condition is
underdiagnosed in research studies and in clinical practice.
Embolic obstructions often display an abrupt and convex terminal rather than a tapered stump. Sometimes, a
contrast silhouette outlines the thrombus (Fig. 8.3C/D). The presence of multiple such occlusions in different vessels
is typical for an embolic shower ( Fig. 8.3A/B). Ultimately, intracoronary imaging may help exclude SCAD, plaque
rupture or erosion as the cause of thrombus formation in atherosclerotic vessels, by demonstrating an intact endo-
thelium without thin cap fibroatheroma [45].
Thrombus is by far the most frequent source of a paradoxical embolic MI. However, paradoxical coronary emboliza-
tions of several other endogenous and iatrogenic materials have been described or anecdotally reported. Paradoxicalgas
embolization is possible among intravenous drug users or with neurosurgery performed in the sitting position [46].A
gaseous embolicMI has been reported in a patient with a PFO as a result of delayed decompression sickness after diving
[47], and in another individual during percutaneous pacemaker lead extraction [48]. Paradoxically embolized foreign
plastic material was found to be causative in a patient suffering MI 10 days after elective hip replacement complicated
by a paraprosthetic fracture [49]. In at least 1 patient, paradoxical neoplasm embolization to the coronary arteries was
described [50]. Paradoxical fat embolism may result from the bone marrow during orthopedic interventions. Similarly,
paradoxical amniotic or placenta embolization could be a source for MI in women in the peripartum period [51]. Finally,
histopathological examination of a coronary thrombus found birefringent microparticles originating from crushed tab-
lets that were intravenously injected by the patient, who was known for illicit drug abuse (unpublished data).
MANAGEMENT OF PATIENTS WITH MYOCARDIAL INFARCTION ATTRIBUTABLE TO
PARADOXICAL CORONARY EMBOLISM
The initial management of coronary embolism is in line with acute coronary syndromes from atherosclerosis
because the acute presentation is similar and includes monitoring, pain relief, administration of antip latelet
medications, and emergency coronary angiography.
Thrombus aspiration may be considered for 3 reasons in patients with embolic MI, especially in the presence of
high thromboembolic burden [11]. First, aspiration thrombectomy reduces the amount of thrombotic material that
may embolize to the distal part of the coronary circulation, decreasing the risk of further microvascular myocardial
damage. Second, aspirated material can be assessed histologically, which may help to determine the origin of the
thrombus or the identification of nonthrombotic embolism [51]. Paradoxical emboli usually show organization of
the thrombotic material as compared to arterial thrombi, which are mostly rich in platelets and fibrin. In rare cases,
pathologic examination may prove that embolism arises from a neoplasm, foreign material, infection, or another rare
source [13]. Finally, removal of thrombotic material allows a better assessment of the underlying coronary artery, by
either conventional angiography or intracoronary imaging such as intravascular ultrasound or optical coherence
tomography; plaque rupture or erosion at the site of the thrombus proves an atherosclerotic cause, and detection
of intramural hematoma or an intimal-medial flap confirms SCAD.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
MANAGEMENT OF PATIENTS WITH MYOCARDIAL INFARCTION ATTRIBUTABLE TO PARADOXICAL CORONARY EMBOLISM 105
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Besides antiplatelet medication and heparin or bivalirudin, glycoproteinIIb/IIIa antagonists may be required dur-
ing percutaneous coronary intervention, especially in patients with a reduced Thrombolysis in Myocardial Infarc-
tion flow <3, which often comes from distal embolization of thrombotic material. On the other hand, balloon
angioplasty and stent implantation is usually not required, if the coronary artery appears normal after successful
removal, fragmentation, or dissolution of embolic material, or is not feas ible due to small vessel diameter in case
of distal embolization. In 1 cohort study, 42% of such patients were treated conservatively [11]. Lon g-term treatment
and secondary prophylaxis depends on the etiology and coexistence of atherosclerotic coronary artery disease [13].
After acute coronary revascularization, patients must be screened for the embolic source and for other systemic
embolism. Right heart catheterization, for the identification and immediate percutaneous closure of a PFO, is feasible
at the time of the index angiography in patients with suspected paradoxical embolism. At the end of the coronary
intervention, it takes less than 15 additional minutes to screen invasively for a PFO and to close it if present. In
contrast to elective PFO closure where a wire or catheter is passed blindly through the PFO, it is recommended
to first perform a right atrial contrast medium injection from a distance in a left anterior oblique view to exclude
a thrombus stuck in the PFO in light of the acute embolic event. The anatom y of a PFO can also be assessed on
that occasion to select the device size without need for echocardiography (Chapter 3).
Follow-up diagnostics include a TEE, the search for atrial fibrillation with repeated ambulatory cardiac rhythm
monitoring, and prior prothrombotic conditions, whereas routine thrombophilia testing is not recommended, as
it is unlikely to change the management of the patient [13]. TEE allows detection of valvular pathologies, intracardiac
thrombi, especially left ventricular thrombus (mural thrombus in dilated cardiomyopathy or postinfarction left
ventricle aneurysm, or left ventricular noncompaction), and left atrial appendage thrombus. It is also the best
technique to identify a not yet occluded PFO with a bubble test or document an atrial septal defect (Chapter 2).
Other diagnostic modalities to detect venoart erial shunts carry a low sensitivity to prove a PFO (transthoracic
echocardiography 47% [52]) or do not provide anatomical information (transcranial Doppler sonography). In the
presence of a venoarterial communication, screening for deep vein thrombosis or pulmonary embolism may be
considered to support the diagnosis of paradoxical embolism.
SECONDARY PREVENTION AFTER PARADOXICAL EMBOLIC MYOCARDIAL
INFARCTION IN THE PRESENCE OF A PFO
Patients with an embolic MI are at increased risk for inherent or later additional embolic ischemic events. Shibata
et al. found simultaneous embolization in 23% of patients with coronary embolism (most were cerebral, followed by
peripheral, renal, and splenic). During a median follow-up of 49 months, 10% of patients had recurrent ischemic events
(4.2% MI, 6.3% stroke). Similarly, cases of patients with coronary embolism and simultaneous [53] or subsequent par-
adoxical arterial embolization [54] have been reported. The prevention of recurrent paradoxical arterial embolization is
of utmost importance. From a pathophysiological standpoint, the administration of antithrombotic medication to
inhibit the development of venous thromboembolism, closure of the venoarterial connection, or a combination of
both are options to prevent potentially fatal further ischemic events. When discussing secondary prevention with a
patient, the physician needs to provide an overview of the risks, costs, and benefits of both treatment options (medical
treatment alone or percutaneous PFO closure), tailored to the individual patient [15].However,evidenceonsecondary
prevention after paradoxical coronary embolism is scarce and must mainly be adapted from trials evaluating treat-
ment strategies in PFO patients with so-called cryptogenic stroke (Chapter 6) (Chapter 7).
For most patients with coronary embolism, oral anticoagulation is empirically recommended as the mainstay
of secondary prophylaxis. Patients with reversible risk factors for thromboembolic disease should receive oral anti-
coagulation for at least 3 months. For those with atrial fibrillation or without reversible risk factors, long-term oral
anticoagulation should be advocated. The combination of antiplatelet therapy with anticoagu lation for a few months
is standard in patients who underwent stent implantation [13], but triple therapy should be avoided.
However, oral anticoagulation has several shortcomings. It bears the risk of increased bleeding, especially in
combination with antiplatelet therapy. On the other hand, oral anticoagulation is often discontinued for several
reasons (forgotten by the patient, interrupted for invasive procedures, discontinued due to bleeding risk [55]),
leaving the patient unprotected from venous thromboembolism with the risk of recurrent paradoxical arterial embo-
lization. Consequently, prescribing oral anticoagulation may not always be sufficient. In a cohort study of 52 patients
with embolic MI, Shibata et al. reported recurrent ischemic events in 5 patients (10%), all of whom were on oral anti-
coagulation for atrial fibrillation but with an inadequate international normalized ratio. Similarly, this can happen to
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
8. MYOCARDIAL INFARCTION AND PFO106
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patients with paradoxical embolism via PFO [54]. Finally, oral anticoagulation does not protect from nonthrombotic
emboli (as for example gas embolization in decompression sickness) [47].
As compared to lifelong oral anticoagulation, PFO closure is a once in a lifetime intervention, with no compliance
concerns. Percutaneous PFO device closure is a routine, low-risk intervention that can be easily performed by a sin-
gle operator via a femoral venous access with a local anesthetic, and the patient can leave the hospital a few hours
later without any physical restrictions [15,56].
CONCLUSIONS
Cardioembolic MI is a common and highly underdiagnosed entity. The most frequentreasonsare atrial fibrillation or
a PFO. In the presence of atherosclerosis, it is a common mistake to ignore the possibility that the MI could be due to a
paradoxical embolus and this accountsfor most of the missed diagnoses.SCAD is probably also erroneously assumedin
many MIs caused by embolism. A PFO should be soughtin all these cases. In the absence of other culprits, PFO closureis
effective and may obviate long-term blood thinners.In the presence of other possible causes of MI (e.g., atherosclerosis),
a PFO should stillbe looked for and closed if found, in additionto the therapies requiredfor the other conditions. Even in
the case of concomitant atrial fibrillation, PFO closure should be considered. Oral anticoagulation does not prevent all
paradoxical embolisms, carriesa cumulative annual bleeding risk, must be stopped for procedures and surgeries(when
risk of paradoxicalembolismis highest),andhas a compliance problem of taking pills every day. Hence, PFO closureasa
once in a lifetime intervention, although it has not been studied in paradoxical coronary embolism, should be offered to
all patients with MI from a paradoxical embolic cause to prevent potentially fatal recurrent events. Device closure must
strongly be recommended as a secondary prevention measure in young patients, as it allows avoidance of oral antico-
agulationfor decades; it should also be offeredfor patients who are unable to tolerate oral anticoagulation due to a high
bleedingriskor other contraindications, including female patients planning to have children.Collateral benefits, such as
protection against other paradoxical embolisms and improvement of migraine headache, diving, mountain climbing,
hypoxemia (in some cases), and improved exercise tolerance represent a welcome bonus (Chapter 18).
References
[1] 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(1):17e20.
[2] 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(19):1946e51.
[3] Wahl A, Ju
¨
ni 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(6):803e12.
[4] Kizer JR, Devereux RB. Clinical practice. Patent foramen ovale in young adults with unexplained stroke. N Engl J Med 2005;353(22):2361e72.
[5] Meier B. Closure of the patent foramen ovale with dedicated Amplatzer occluders: closing in on a mechanical vaccination. Cathet Cardiovasc
Interv 2008;72(1):80e1.
[6] Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. Antiplatelets after stroke. N Engl J Med 2017;
377(11):1011e21.
[7] Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017;
377(11):1033e42.
[8] Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 2017;
377(11):1022e32.
[9] Willey V, Franchino-Elder J, Fu AC, et al. Treatment and persistence with oral anticoagulants among newly diagnosed patients with
non-valvular atrial fibrillation: a retrospective observational study in a US commercially insured and Medicare Advantage population.
BMJ Open 2018;8(6):e020676.
[10] Prizel KR, Hutchins GM, Bulkley BH. Coronary artery embolism and myocardial infarction. Ann Intern Med 1978;88(2):155e61.
[11] Shibata T, Kawakami S, Noguchi T, et al. Prevalence, clinical features, and prognosis of acute myocardial infarction attributable to coronary
artery embolism. Circulation 2015;132(4):241e50.
[12] Charles RG, Epstein EJ. Diagnosis of coronary embolism: a review. J R Soc Med 1983;76(10):863e9.
[13] Raphael CE, Heit JA, Reeder GS, et al. Coronary embolus: an underappreciated cause of acute coronary syndromes. JACC Cardiovasc Interv
2018;11(2):172e80.
[14] Popovic B, Agrinier N, Bouchahda N, et al. Coronary embolism among ST-segment-elevation myocardial infarction patients: mechanisms
and management. Circ Cardiovasc Interv 2018;11(1):e005587.
[15] Windecker S, Stortecky S, Meier B. Paradoxical embolism. J Am Coll Cardiol 2014;64(4):403e15.
[16] Cheng TO. Coronary embolism. Int J Cardiol 2009;136(1):1e3.
[17] Pilgrim T, Meier B, Khattab AA. Death by patent foramen ovale in a soccer player. J Invasive Cardiol 2013;25(3):162e4.
[18] Carano N, Agnetti A, Hagler DJ, Tchana B, Squarcia U, Bernasconi S. Acute myocardial infarction in a child: possible pathogenic role of patent
foramen ovale associated with heritable thrombophilia. Pediatrics 2004;114(2):e255e258.
[19] Dao CN, Tobis JM. PFO and paradoxical embolism producing events other than stroke. Cathet Cardiovasc Interv 2011;77(6):903e9.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
REFERENCES 107
https://t.me/med1917
[20] Wo
¨
hrle J, Kochs M, Hombach V, Merkle N. Prevalence of myocardial scar in patients with cryptogenic cerebral ischemic events and patent
foramen ovale. JACC Cardiovasc Imag 2010;3(8):833e9.
[21] Merghani A, Maestrini V, Rosmini S, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low
atherosclerotic risk profile. Circulation 2017;136(2):126e37.
[22] Stortecky S, Cook S, Meier B, Togni M. Patent foramen ovale: a culpable pathway for myocardial infarction. J Am Coll Cardiol 2011;58(18):1923.
[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(9601):1773e9.
[24] Lowe GD. Is venous thrombosis a risk factor for arterial thrombosis? Lancet 2007;370(9601):1742e4.
[25] 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.
[26] Tukaye DN, Cavallazzi RS. Paradoxical thromboembolism/ST-elevation myocardial infarction via a patent foramen ovale in sub-massive
pulmonary embolism following an upper extremity deep venous thrombosis: is it time for a change in the standard of care? Cardiol Res
2014;5(3e4):112e7.
[27] Abecasis J, Ribeiras R, Gabriel HM, Andrade MJ. Thrombus entrapment: the clue for coronary embolism. Eur Heart J 2014;35(42):2971.
[28] Kearney LG, Srivastava PM. Thrombus entrapped in a patent foramen ovale: a potential source of pulmonary and systemic embolism. Heart
Lung Circ 2010;19(1):58e60.
[29] Pavoni D, Zanuttini D, Spedicato L, Mazzaro E, Ugolino L. Large interatrial thrombus-in-transit resulting in acute myocardial infarction
complicated by atrioventricular block and cardiogenic shock. J Am Coll Cardiol 2012;59(14):1329.
[30] Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988;318(18):1148e52.
[31] Crump R, Shandling AH, Van Natta B, Ellestad M. Prevalence of patent foramen ovale in patients with acute myocardial infarction and
angiographically normal coronary arteries. Am J Cardiol 2000;85(11):1368e70.
[32] Sastry S, Riding G, Morris J, et al. Young Adult myocardial infarction and ischemic stroke: the role of paradoxical embolism and thrombo-
philia (the YAMIS study). J Am Coll Cardiol 2006;48(4):686e91.
[33] Meier B, Kalesan B, Mattle HP, et al. Percutaneousclosure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013;368(12):1083e91.
[34] 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(20):
2335e42.
[35] 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(11):991e9.
[36] 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(26):2029e36.
[37] 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(22):2766e74.
[38] Saw J. Coronary angiogram classification of spontaneous coronary artery dissection. Cathet Cardiovasc Interv 2014;84(7):1115e22.
[39] Tweet MS, Gulati R, Williamson EE, Vrtiska TJ, Hayes SN. Multimodality imaging for spontaneous coronary artery dissection in women.
JACC Cardiovasc Imaging 2016;9(4):436e50.
[40] Saw J, Mancini GBJ, Humphries KH. Contemporary review on spontaneous coronary artery dissection. J Am Coll Cardiol 2016;68(3):297e312.
[41] Saw J, Humphries K, Aymong E, et al. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol
2017;70(9):1148e58.
[42] Agewall S, Beltrame JF, Reynolds HR, et al. ESC working group position paper on myocardial infarction with non-obstructive coronary
arteries. Eur Heart J 2017;38(3):143e53.
[43] Anderson FA, 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(5):933e8.
[44] Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor
categories. Circulation 1998;97(18):1837e47.
[45] Iannaccone M, Montefusco A, Omede P, D’ascenzo F, Moretti C. All that glitters ain’t gold! A case of embolic STEMI demonstrated by OCT.
Int J Cardiol 2015;196:14e5.
[46] Fathi AR, Eshtehardi P, Meier B. Patent foramenovaleand neurosurgery in sitting position:a systematic review. Br J Anaesth 2009;102(5):588e96.
[47] Schneeweis C, Fleck E, Gebker R. Myocardial infarction after scuba diving. Eur Heart J 2012;33(17):2224.
[48] Arnott C, Kelly K, Wolfers D, Cranney G, Giles R. Paradoxical cardiac and cerebral arterial gas embolus during percutaneous lead extraction
in a patient with a patent foramen ovale. Heart Lung Circ 2015;24(1):e14e
17.
[49] Mallouppas M, Vassiliou V, Goddard M, Rana B, Braganza D. An unusual complication of hip surgery: paradoxical coronary embolism of
foreign material as a cause of acute MI. EuroIntervention 2015;11(6):658.
[50] Diaz Castro O, Bueno H, Nebreda LA. Acute myocardial infarction caused by paradoxical tumorous embolism as a manifestation of
hepatocarcinoma. Heart 2004;90(5):e29.
[51] Ra
¨
ber L, Meier B, Steiger VS, Gugger M, Vogel R. Peripartal myocardial infarction caused by placenta embolus. Circulation 2011;124(2):e26e27.
[52] Di Tullio M, Sacco RL, Venketasubramanian N, Sherman D, Mohr JP, Homma S. Comparison of diagnostic techniques for the detection of a
patent foramen ovale in stroke patients. Stroke 1993;24(7):1020e4.
[53] Grogono J, Fitzsimmons SJ, Shah BN, Rakhit DJ, Gray HH. Simultaneous myocardial infarction and ischaemic stroke secondary to paradoxical
emboli through a patent foramen ovale. Clin Med 2012;12(4):391e2.
[54] Garachemani A, Eshtehardi P, Meier B. Paradoxical emboli through the patent foramen ovale as the suspected cause of myocardial and renal
infarction in a 48-year-old woman. Cathet Cardiovasc Interv 2007;70(7):1010e2.
[55] Namasivayam M, Spina R, Bobillo L, Feneley MP, Baron DW. Acute myocardial infarction due to paradoxical embolism. Int J Cardiol 2016;
209:190e1.
[56] Nietlispach F, Meier B. Percutaneous closure of patent foramen ovale: an underutilized prevention? Eur Heart J 2016;37(26):2023e8.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
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CHAPTER
9
Peripheral Embolism and PFO
Dhaval Kolte, Ignacio Inglessis, Sammy Elmariah
Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
OUTLINE
Introduction 109
Epidemiology 109
Clinical Presentation 110
Diagnosis 110
Management
111
Summary
112
References
112
INTRODUCTION
In 1877, Cohnheim described the first case of “paradoxical embolism,” a term that was later coined by Zahn in
1885 to describe a condition where thrombus from the venous system enters into the arterial system via an abnormal
communication between the chambers of the heart, which in most cases was found to be a patent foramen ovale
(PFO) [1]. Over the past 2 decades, there has been a tremendous interest in understanding the role of PFO in the
pathogenesis of stroke and transient ischemic attack (TIA) (Chapters 4e7), myocardial infarction (Chapter 8),
migraine with aura (Chapters 10 and 11), and hypoxemia (Chapter 12), as well as in examining the safety and effi-
cacy of transcatheter device closure of PFO for the treatment of these conditions [2e4]. However, the passage of
thrombus through a PFO, as a potential mechanism for systemic noncerebral embolism, remains poorly evaluated.
Although paradoxical peripheral em bolism of clinical significance occurs much less frequently than cryptogenic
stroke (also called embolic stroke of undetermined source [ESUS]) in patients with PFO, it can result in life- or
limb-threatening conditions such as acute myocardial infarction (Chapter 8) or acute limb ischemia. The current
chapter will specifically review the epidemi ology, clinical presentation, diagnosis, and management of paradoxical
peripheral embolism in patients with PFO.
EPIDEMIOLOGY
The majority of peripheral emboli arise from the left side of the heart, with paradoxical embolism being a far less
common source/mechanism. In a series of 406 patients with peripheral emboli, the source was identified as probable
paradoxical embolism (defined as presence of all 3 criteria of Johnson ’s triad: venous thrombus with or without pul-
monary embolism, intracardiac defect with right-to-left shunting, and peripheral arterial embolization) in 6 (2%) pa-
tients and possible paradoxical embolism (defined as presence of 2 of the 3 Johnson’s criteria) in 8 (2%) patients,
whereas 82 (20%) patients had an unknown source or incomplete workup; the remaining peripheral emboli were
from cardiac (61%) and arterioarterial (15%) sources [5]. Patients with paradoxical peripheral embolism were
younger compared to those with other forms of arterial thromboembolism (mean age 39 vs. 68 years) [5].
109
PFO Closure for Stroke, Myocardial Infarction, Peripheral Embolism, Migraine, and Hypoxemia
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PFO is commonly present in patients with cryptogenic stroke, with a reported prevalence up to 54% in
patients <55 years of age [6]. However, the exact prevalence of PFO in patients with peripheral arterial embolism
is not known. A multicenter study from the United Kingdom demonstrated a prevalence of 20%, which is no
higher than the frequency of PFO found in the general population (w24%) [7,8].Inthisstudy,15outof71patients
(mean age 65.1 years, 62% men) with a diagnosis of peripheral arterial embolism, who w ere initially suspected to
have a PFO based on clinical findings, were selected for additional testing. On transcranial Doppler assessment of
the cerebral circulation with an agitated saline bubble study, 12 of the 15 patients were found to have no PFO, and 3
of the 15 (20%) had already undergone transcatheter PFO closure [7]. In another study from the United Kingdom,
10 patients were referred for intestinal transplantation for short gut syndrome secondary to previous acute supe-
rior mesenteric artery occlusion and intestinal ischemia; of these, 80% (8/10) were found to have PFO [9].
PFO-mediated paradoxical embolism most commonly presents as cryptogenic stroke or ESUS. Systemic,
noncerebral or extracerebral embolism occurs much less frequently, accounting for 5%e10% of all paradoxical emb-
olisms [10]. It is unclear why the majority of paradoxical embolism cases associated with PFO present as strokes. The
brain receives about 15% of the systemic output but it is more susceptible to small emboli than the rest of the body,
save for the eye and the coronary arteries. There are likel y many small noncerebral emboli to different parts of the
body that may remain asymptomatic and hence undiagnosed. It is hypothesized that the true prevalence of PFO-
mediated cerebral events or myocardial infarction from small emboli is underestimated in research studies and clin-
ical practice. In addition, older patients with venous insufficiency are more likely to have venous thrombosis with
paradoxical embolism. Thus, the true incidence of cerebral, coronary, or peripheral embolism in patients with PFO is
unknown. Prior studies have shown that w1%e7.5% of patients with a known diagnosis of PFO present with pe-
ripheral embolism as the index event [11e15]. In a large study of 800 patients who underwent PFO closure between
January 1995 and May 2010 at Massachusetts General Hospital, the indication for device closure was peripheral em-
bolism in 22 (2.8%) patients, 3 of whom also had a stroke [11]. Similarly, in another single- center study from the
United States, of 416 patients referred for evaluation of PFO-related conditions from 2001 to 2009, 12 presented
with noncerebral systemic embolism (8 [1.9%] with myocardial infarction and 4 [0.96%] with peripheral arterial em-
bolism) [12]. Studies from outside the United States have demonstrated a similar or higher incidence of paradoxical
peripheral embolism in patients with PFO [13e15]. In a single-center study from Italy, of 150 patients referred for
transcatheter closure of a PFO or atrial septal defect, 4 (2.7%) had a history of acute lower limb ischemia [13].In
the multicenter Clinical Trial Comparing Percutaneous Closure of PFO Using the Am platzer PFO Occluder with
Medical Treatment in Patients with Cryptogenic Embolism (PC trial), of the 414 patients randomized to either
PFO closure (n ¼ 204) or medical therapy (n ¼ 210), peripheral embolism was the index event in 11 patients
(2.7%) (Chapter 6) [14]. On the other hand, in a single-center study from Switzerland, of 80 patients who underwent
PFO closure, peripheral embolism was the index thromboembolic event in 6 patients (7.5%) [15].
CLINICAL PRESENTATION
When symptomatic, PFO-mediated paradoxical embolism involving the peripheral arteries frequently presents as
acute lower limb ischemia, typically involving the femoropopliteal arteries. However, other clinical presentations
can also occur and have been described in the literature. In a case-series of 5 consecutive patients with acute limb
ischemia and PFO, 2 had acute limb-threatening ischemia involving the upper extremity due to embolic
occlusion of the subclavian and/or brachial arteries [16]. In a single-center American study, 4 out of 416 patients
referred for eva luation of PFO-related conditions presented with peripheral embolism involving the popliteal artery
(n ¼ 1), ophthalmic artery (n ¼ 2), or brachial artery (n ¼ 1) [12]. Other presentations including renal infarction,
splenic infarction, acute mesenteric ischemia, and acute Leriche syndrome (aortoiliac occlusive disease) have also
been described in case reports [17e22].
DIAGNOSIS
The clinical triad of paradoxical embolism was first described by Johnson [1] and included presence of (1) deep
venous thrombosis (DVT) and/or pulmonary embolism, (2) an intracardiac defect that permits right-to-left shunt-
ing, and (3) arterial embolism not arising from the left side of the heart. A fourth criterion was later described by
Loscalzo [23] and included the presence of a favorable pressure gradient promoting right-to-left shunting. It is
well established, however, that a DVT may be clinically occult and not detectable in more than 40% of patients
9. PERIPHERAL EMBOLISM AND PFO110
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with paradoxical embolism [24]. Nonetheless, prior studies have shown that nearly one-third of DVTs are recurrent,
and that patients with DVT are more likely to have a history of systemic thromboembolism compared to those
without DVT [25]. Thus, a clinical history of DVT and the onset of symptoms associated with a Valsalva maneuver
may be the first clue to the diagnosis of paradoxical embolism.
The Risk of Paradoxical Embolism (RoPE) score is a guide used to indicate whether a PFO associated with a cryp-
togenic stroke is causally related or an incidental finding [26]. Scores range from 0 to 10, with larger values represent-
ing a higher probability that a PFO is related to the stroke. However, the RoPE score has not been validated in patients
with systemic noncerebral embolism who are found to have a PFO. The RoPE score is discussed in detail in Chapter 4.
In patients presenting with acute peripheral arterial ischemia, we propose the following algorithm (Fig. 9.1)to
establish a diagnosis of paradoxical embolism: (1) exclude intracardiac (cardioembolic) source (e.g., atrial fibrillation
or flutter, left atrial appendage thrombus, left ventricular thrombus, infective endocarditis, nonbacterial thrombotic
endocarditis, rheumatic mitral stenosis, prosthetic heart valve, atrial myxomas), (2) exclude native arterial ischemia
(e.g., peripheral artery disease, aneurysm, dissection, trauma, vasculitis, iatrogenic injury, hypercoagulability), and
(3) establish presence of PFO with evidence of right-to-left shunt and define high-risk features (e.g., atrial septal aneu-
rysm, large shunt). The presence of concomitant DVTor pulmonary embolism would further support the diagnosis of
paradoxical peripheral embolism; however, its absence does not exclude this diagnosis. It is possible to have more than
1 competitive cause of ischemia. Some physicians screen for a PFO or pulmonary right-to-left shunt in patients with
peripheral embolism and close it when found in an attempt to treat all potential causes of thromboembolism.
MANAGEMENT
The management of patients with peripheral embolism and PFO is twofolddthe initial treatment of the acute
presentation (e.g., acute limb ischemi a), and long-term therapy for secondary prevention of recurrent paradoxical
embolism. The initial treatment depends on the presentation but involves systemic anticoagulation, catheter-
directed thrombolysis, endovascular or surgical thrombo-embolectomy and revascularization, or amputation [27].
FIGURE 9.1 Proposed Algorithm for Evaluation and Management of Paradoxical Peripheral Embolism Associated With a PFO. LAA, left atrial
appendage, LV, left ventricle, PAD, peripheral arterial disease, PFO, patent foramen ovale.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
MANAGEMENT 111
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