5. DEFINITION:
Cryptogenic ischaemic left circulation embolisms
are defined as :
any definite ischemia (symptomatic or
asymptomatic) occurring in an arterial bed which
lacks a known cause despite investigation.
Patients presenting with this clinical picture should be
screened for the presence or absence of a PFO.
6. PFO Agenda
1. Diagnosis of PFO
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure.
7. 1
1. Diagnosis of PFO.
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure
8. 1-Diagnosis of PFO
Aim:
The diagnosis of PFO is required for deciding on a
PLAN of treatment.
Several imaging techniques can be used for
PFO detection, including echocardiography –
transthoracic (TTE) and transoesophageal (TEE), and
transcranial Doppler ultrasonography (TCD
10. C-TTEc-TTE is a reliable, feasible,
cheap, non-invasive
technique
that enables PFO detection
with high specificity,
therefore
useful as first-line test for
screening a PFO
when c-TTE study is
negative or images are
inadequate but the
index of suspicion is
high………..
11.
12. C-TCD
•Non –invasive.
•A recent meta-analysis
demonstrated mean
sensitivity of
97% and specificity of 93%
for c-TCD in comparison
with c-TEE.
•The effectiveness of
Valsalva can be easily
verified throughout the test
17. PFO variables to be assessed for decision
making and interventional treatment
PFO morphology: size, location, length of the tunnel
Spatial relationship and distances between the PFO and the
aortic root, vena cava, valves and the free walls of the
atrium
•Comprehensive evaluation of the atrial septum, including
inspection for atrial septal aneurysms, movement, and other
atrial septal defects
Presence/absence of a Eustachian valve and/or Chiari
network
Thickness of the septum primum and secundum
Color Doppler evaluation of the shunt at rest and after a
Valsalva manoeuvre
18.
19.
20.
21.
22. 2-
1. Diagnosis of PFO.
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure
23. 2- Assessment of the role of PFO in
the left circulation embolism.(LCE)
A PFO is seen in 25% of the
general population and may
therefore coexist by chance in a
patient with an unexplained left
circulation embolism.
24. No single clinical, anatomical or imaging
characteristics are sufficient to make a quantitative
estimation of the probability of a PFO causal role
When a PFO is considered to play a pathogenic role
in an embolism, the episode should not be classified
as cryptogenic anymore
The presence of other risk factors does not exclude
a causative role of PFO.
25. Additional tools to evaluate PFO may be
useful in helping to determine whether an
observed PFO is incidental or
pathologically related to stroke.*
ie …..Is it really cryptogenic or
PFO –Related stroke?
*Die Tullio MR et al,J am coll cardiol2013;62:35-41
26. 3-
1. Diagnosis of PFO.
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE.
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure
27. 3-Assessment of the likelihood of
PFO in the left circulation
embolism.(LCE(
We need to identify which
PFO patients are more likely
to have paradoxical embolism.
28.
29. Patient characteristics:
A meta-analysis of observational studies showed a
stronger relative association of PFO with cryptogenic
stroke in patients <55 years as compared to older .*
The presence of other co morbidities or clinical risk
factors for stroke does not, per se, exclude a
pathophysiological role of PFO in cryptogenic
embolism, though their absence increases the
likelihood of its pathogenic role.
*Alsheikh-Ali AA, Thaler DE, Kent DM. Patent foramen ovale in cryptogenic stroke: Incidental or
pathogenic? Stroke. 2009;40:2349–55.
30. Stroke pattern:
Neither the localization nor type of infarct pattern in grey
or white matter was specific for PFO embolism in
observational studies.
Cortical infarcts are usually considered embolic but a
recent patient-level meta analysis of RCTs suggests that
non-cortical infarcts can also have an embolic origin.
Kent DM, Dahabreh IJ, Ruthazer R, Furlan AJ, Reisman M, Carroll JD, Saver JL, Smalling
RW, Jüni P, Mattle HP, Meier B, Thaler DE. Device Closure of Patent Foramen Ovale
after Stroke: Pooled Analysis of Completed Randomized Trials. J Am Coll Cardiol.
2016;67
31. Clinical clues:
Simultaneous or previous occurrence of pulmonary
emboli.
Documentation of a venous source of embolism
around the time of stroke.
Immobilization, recent major surgery, or an extended
car or airplane journey implies possible venous clot
development.
Activity at the time of the stroke is also relevant –
straining manoeuvres,
obstructive sleep apnoea
Waking up with stroke.
32. ROPE Score:*
It is a clinical-determined score called Risk Of
Paradoxical Embolism score.
It provides a reliable clinical tool to assess probability
to find a PFO in a patient with cryptogenic stroke & a
probability for recurrent stroke related to paradoxical
embolization through PFO.
*Kent DM,Thaler DE RoPE Study investigators.
33. Variables of RoPE score:
Young age
Presence of cortical stroke
Absence of DM,Hypertenson,smoking and prior
stroke or TIA.
10 points are derived from theses variables.
RoPE score : 0-3…PFO-attributable risk 0% (95% CI:0-
4)
RoPE score :9-10…PFO attributable risk 88%
(95%CI:83-91)
Easy applicable, but not taking in account antaomy of
PFO ,hemodynamic of shunt
35. PFO Characteristics :
Dangerous PFO…..!
Large PFO.*
Association with IAS Aneurysm.*
Long Eustechian valve.
Long PFO tunnel.
Basal right to left shunt.
*Meiere B,Nietlispach F,Eeuropean Heart Journal 2018;39:1650-1652
36. 4-
1. Diagnosis of PFO.
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE.
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure
37. 4-Assessment of risk of recurrence
in PFO-mediated LCE
Meta-analyses of observational and/or randomised
studies suggest that the annual recurrence rate on
medical therapy ranges from 0% -14 % for stroke .*
Some predictors of stroke recurrence have been
identified prospectively and retrospectively.
38. Some predictors of stoke recurrence:
Atrial septal aneurysm anatomy is particularly
predictive.
In one study, a high D-dimer level on admission was
an independent predictor of recurrent ischaemic
stroke in patients with PFO.*
*Thaler DE, Ruthazer R, et al. Recurrent stroke predictors differ in medically treated patients
with pathogenic vs other PFOs. Neurology. 2014;83:221–6
39. 5-
1. Diagnosis of PFO.
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE.
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure
40. 5-Efficacy and safety of medical
therapy
In recent meta-analysis of the RCTs, the incidence of
recurrent stroke on medical therapy was 4.6% after
3.8 years of follow-up .
No drug therapy can be considered as a …
(gold standard).
Latest AHA/ASA guidelines (2014) discuss this entity.
41.
42. 6-
1. Diagnosis of PFO.
2. Assessment of the role of PFO in the left circulation
embolism.(LCE)
3. Estimation of the likelihood of a PFO-mediated
LCE.
4. Evaluation of risk of recurrence of PFO-mediated
LCE
5. Medical therapy in PFO-mediated LCE
6. Safety and efficacy of PFO closure
43. 6-Safety and efficacy profile of
PFO closure
From multiple Randomized trials….Primary technical
success approaches 100%.
complete closure is seen in 93-96% at one year.
Individual randomized data show a relative risk
reduction of (RRR) up to 80% for recurrent strokes.*
One meta-analysis of RCTs has shown the stroke
recurrence rate to be 0.29 per 100 person years.**
* Meier B, Kalesan B,et al. Percutaneous closure of patent foramen ovale in cryptogenic
embolism. PC trial. N Engl J Med. 2013;368:1083–91.
** Wahl A, Jüni P, 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.
44. Recently published RCT :
ClOSURE I, PC Trial ,RESPECT…
Although…..
PFO closure showed a nominal 38% reduction in the
hazard of recurrent stroke, this was without statistical
significance compared to medical therapy
51. More recent randomized
studies…..
CLOSE …(PFO closure or anticoagulants versus
antiplatelet therapy to prevent stroke recurrence)
DEFENSE-PFO…(Device closure versus medical
therapy for cryptogenic stroke patients with high risk
PFO)
GORE REDUCE…(GORE Septal occluder device for
PFO closure in stroke patients.
52.
53.
54.
55.
56. Problems with PFO closure…
.
The use of larger devices has a higher risk of residual
shunts.
Atrial arhythmias
Device embolisation
Device thrombosis
Endocarditis
57. Medical therapy &follow up after
closure:
Dual antiplatelet therapy (Aspirin 100 mg and
clopidogrel 75mg ) is required after the procedure.
No data to guide the duration of antiplatelet, most
operators recommend therapy for 3-6 months.
TTE with bubble contrast 6-12 months post
procedure.
59. PFO & Migraine
There is an association between PFO and migraine .but it is
unclear if there is a causal relationship or if it is only
comorbidity.
One possible mechanism of explaining how RLS may play a role
in MA is related to the occurrence of subclinical emboli and/or
higher concentrations of serotonin and other metabolites that
avoid the lungs and directly enter the systemic circulation,
causing irritation of the trigeminal nerve and brain
vasculature, triggering migraine.
An important role of ASA, beyond PFO, in the genesis of aura
has been previously
Recently, the relationship between migraine and PFO has been
investigated .
On the contrary, the prevalence of PFO in patients with
migraine without aura is similar to that of healthy population.
62. MANAGEMENT OF PATIENTS WITH CRYPTOGENIC
STROKE AND PATENT FORAMEN OVALE
Clinical risk fa c tors
Mu ltiple i sch e mic lesions on CT/ MR
Re cu rre nt clinical e ve nts
History of D VT/ PE and/o rThro mb ophilia
Valsalva-a sso ciated e mb olic e ve nt
I sch e mic eve nt on arou sal )O SAS(
Long tra vel/i mmo bilization a sso ciated e ve nt
Si multaneous syst e mic/pul mo rany e mb olism
Cryptogenic Str oke /TIA ) sympto matic/asympto matic (
& PF O with R -L Sh un t
Firs t cry p to ge nic event
wi th out a na to mical/ clinical
risk fa c tors
Any cry p to ge nic e vent
(fi rs t or recurrent ( on
AP and/or OA th era py
Me dical th era py
C a th PF O closure
as a n al ternative
t o medical th era py
C a th PF O clo sure
Ana to mical risk fa c tors
Atrial se ptal aneu rysm
Large PF O <(4 mm(
Ba sal R -L sh unt
Eu stachian valve <1 0 mm
Chiari netwo rk
Long PF O tunnel
66. Conclusion &Take Home Message
Several elements are needed to be accurately
researched prior accusing PFO to be guilty in
challenging syndromes that could be PFO-related.
A logical approach should be designed for each
patient.
PFO
67. Over –simplification of PFO management cannot be
assumed with a standard common plan for every
patient.
Patient with PFO would refer to a brain-heart team
for a joint evaluation of individual cases in order to
get to personalized choices which take into account
neurological and cardiological aspects (clinical,
imaging, and interventional).