Patent Foramen Ovale and Cryptogenic Stroke: Challenges in Diagnosis and Management

A patent foramen ovale (PFO) is a common disorder that affects between 20-34% of the adult population. This condition is a benign finding for most people. However, In some the PFO can open widely and enabling paradoxical embolism to transit from venous to arterial circulation, which is associated with stroke and systemic embolization. There are still unclear to date regarding the effectiveness of pharmacological anticoagulant therapy, defined as antithrombin or antiplatelet therapy, which has proven to be more beneficial for patients with PFO and cryptogenic stroke. In addition, surgical and transcutaneous PFO closure has been proposed for secondary prevention of stroke in patients with cryptogenic stroke with PFO. Both catheter-based and surgical modes of closure have been shown to reduce the incidence of subsequent embolism substantially. This review will discuss the evidence regarding the relationship between PFO and cryptogenic stroke and decision making for management strategies.

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Patent Foramen Ovale Closure in 2019

Interventional Cardiology Review ◽

10.15420/icr.2018.33.2 ◽

2019 ◽

Vol 14 (1) ◽

pp. 34-41 ◽

Cited By ~ 11

Author(s):

Joel P Giblett ◽

Omar Abdul-Samad ◽

Leonard M Shapiro ◽

Bushra S Rana ◽

Patrick A Calvert

Keyword(s):

Patent Foramen Ovale ◽

Decompression Sickness ◽

Recurrent Stroke ◽

Adult Population ◽

Cryptogenic Stroke ◽

Foramen Ovale ◽

Arterial Circulation ◽

Paradoxical Embolus ◽

Randomised Controlled ◽

Pfo Closure

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people it is a benign finding; however, in some the PFO can open widely, enabling a paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised controlled trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this review considers the evidence for PFO closure in cryptogenic stroke. The review also addresses other potential indications for closure, including systemic embolisation, decompression sickness, platypnoea–orthodeoxia syndrome and migraine with aura. It lays out the pre-procedural investigations and preparation for the procedure. Finally, it gives an overview of the procedure itself, including discussion of closure devices.

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Patent Foramen Ovale, the Role of Antiplatelet Therapy Alone or Anticoagulant Therapy Alone Versus Device Closure for Cryptogenic Stroke: A Review of the Literature and Current Recommendations

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200203111641 ◽

2020 ◽

Vol 18 (2) ◽

pp. 135-150

Author(s):

Harsha S. Nagarajarao ◽

Chandra P. Ojha ◽

Archana Kedar ◽

Debabrata Mukherjee

Keyword(s):

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Narrow Channel ◽

Paradoxical Embolism ◽

Current Evidence ◽

Foramen Ovale ◽

The Right ◽

The Relationship ◽

Current Guidelines

: Cryptogenic stroke and its relation to the Patent Foramen Ovale (PFO) is a long-debated topic. Recent clinical trials have unequivocally established the relationship between cryptogenic strokes and paradoxical embolism across the PFO. This slit-like communication exists in everyone before birth, but most often closes shortly after birth. PFO may persist as a narrow channel of communication between the right and left atria in approximately 25-27% of adults. : In this review, we examine the clinical relevance of the PFO with analysis of the latest trials evaluating catheter-based closure of PFO’s for cryptogenic stroke. We also review the current evidence examining the use of antiplatelet medications versus anticoagulants for stroke prevention in those patients with PFO who do not qualify for closure per current guidelines.

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Risk of Paradoxical Embolism (RoPE)–Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure

Stroke ◽

10.1161/strokeaha.120.029350 ◽

2020 ◽

Vol 51 (10) ◽

pp. 3119-3123

Author(s):

David M. Kent ◽

Jeffrey L. Saver ◽

Robin Ruthazer ◽

Anthony J. Furlan ◽

Mark Reisman ◽

...

Keyword(s):

Relative Risk ◽

Risk Reduction ◽

Patent Foramen Ovale ◽

Relative Risk Reduction ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Attributable Fraction ◽

Patient Specific ◽

Foramen Ovale ◽

Pfo Closure

Background and Purpose: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific “PFO-attributable fraction”—the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. Methods: We pooled data from the 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 Patent Foramen Ovale), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial–compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. Results: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42–1.59] P =0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11–0.85] P =0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P =0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial ( r =0.95, P <0.001) and 2-trial ( r =0.92, P <0.001) analyses. Conclusions: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.

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Patent Foramen Ovale Closure: State of the Art

Interventional Cardiology Review ◽

10.15420/icr.2019.27 ◽

2020 ◽

Vol 15 ◽

Author(s):

Joel P Giblett ◽

Lynne K Williams ◽

Stephen Kyranis ◽

Leonard M Shapiro ◽

Patrick A Calvert

Keyword(s):

Patent Foramen Ovale ◽

Decompression Sickness ◽

Recurrent Stroke ◽

Adult Population ◽

Cryptogenic Stroke ◽

Foramen Ovale ◽

Arterial Circulation ◽

Arterial Embolisation ◽

Randomised Control Trials ◽

Paradoxical Embolus

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people, it is a benign finding; however, in some people, the PFO can open widely to enable paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of the PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised control trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this article considers the evidence for PFO closure in cryptogenic stroke. The article also addresses other potential indications for closure, including systemic arterial embolisation, decompression sickness, platypnoea–orthodeoxia syndrome and migraine with aura. The article lays out the pre-procedural investigations and preparation for the procedure. Finally, the article gives an overview of the procedure itself, including discussion of closure devices.

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Safety and efficacy of endovascular patent foramen ovale closure: the first results of a Russian multicenter study

Neurology neuropsychiatry Psychosomatics ◽

10.14412/2074-2711-2020-6-26-32 ◽

2020 ◽

Vol 12 (6) ◽

pp. 26-32

Author(s):

D. V. Ognerubov ◽

A. S. Tereshchenko ◽

A. N. Samko ◽

G. К. Arutyunyan ◽

O. A. Sivakova ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Young Patients ◽

Paradoxical Embolism ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

History Of ◽

Pfo Closure

Patent foramen ovale (PFO) is detectable in more than 25% of the adult population and is generally clinically insignificant. However, it can be a cause of paradoxical embolism in some cases. Randomized trials indicate that endovascular PFO closure in patients with a history of cryptogenic stroke is an effective method for the secondary prevention of catastrophic brain damage.Objective: to study the safety and efficiency of endovascular PFO closure in young patients with a history of cryptogenic stroke.Patients and methods. Sixty-two patients, including (22 males and 40 females) women, underwent percutaneous PFO closure in May 2018 to March 2020. The patients' mean age was 37.4±7.6 years. The inclusion criteria were a prior cryptogenic ischemic stroke lasting less than 12 months and PFO with a high risk for paradoxical embolism (PFO concurrent with atrial septal aneurysm or hypermobility; PFO, ≥2 mm size; the presence of the Chiari network and/or the Eustachian valve).Results and discussion. The technical success of the operation was achieved in all cases. In 50 (80.6%) patients, the right chamber of the heart was completely isolated from the left one in the first 3 months. During the first year, the atria were also completely isolated in 10 (16.1%) patients. A left-to-right shunt persisted in 2 (3.2%) patents 12 months later. Two patients were found to have main procedural complications: one had perioperative atrial fibrillation and the other had pseudoaneurysm formation at the puncture site.Conclusion. Endovascular PFO closure is a safe and effective operation for the secondary prevention of recurrent ischemic stroke. In our study, blood shunting through the PFO was stopped in 96.6% of patients at less than 6 months after surgery, which suggests that there is a rapid and effective reduction in the risk of paradoxical embolism.

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Cryptogenic Stroke: To Close a Patent Foramen Ovale or Not to Close?

Journal of Central Nervous System Disease ◽

10.1177/1179573518819476 ◽

2018 ◽

Vol 10 ◽

pp. 117957351881947 ◽

Cited By ~ 4

Author(s):

Santhosh J Kottoor ◽

Rohit R Arora

Keyword(s):

Randomized Controlled Trials ◽

Patent Foramen Ovale ◽

Anticoagulation Therapy ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Significant Benefit ◽

Controlled Trials ◽

Foramen Ovale ◽

Randomized Controlled ◽

Pfo Closure

A patent foramen ovale (PFO) has been shown to be highly prevalent in patients diagnosed with strokes of unknown cause, which are also called cryptogenic strokes (CSs). It has been a long-running controversy as to whether a PFO should be closed or not to prevent recurrent strokes in patients diagnosed with CS. A paradoxical embolism that is produced through a PFO is hypothesized to be a leading cause of CS, especially in younger patients with low risk factors for stroke. It remains controversial as to which anticoagulation therapy, defined as antithrombin or antiplatelet therapy, is better for patients with CS and a PFO. In addition, surgical and transcutaneous closure of a PFO has been proposed for the secondary prevention of stroke in patients with CS with PFO. Several randomized controlled trials have been conducted in recent years to test whether a PFO closure gives a significant benefit in the management of CS. Three earlier randomized controlled trials failed to show a statistically significant benefit for a PFO closure; thus, many investigators believed that a PFO was an incidental bystander in patients with CS. However, meta-analyses and more recent specific trials have eliminated several confounding factors and possible biases and have also emphasized the use of a shunt closure over medical therapy in patients with CS. Therefore, these latest studies (the CLOSE and REDUCE trials) can possibly change the treatment paradigm in the near future.

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Patent foramen ovale

Practical Neurology ◽

10.1136/practneurol-2019-002450 ◽

2020 ◽

Vol 20 (3) ◽

pp. 225-233 ◽

Cited By ~ 1

Author(s):

Vafa Alakbarzade ◽

Tracey Keteepe-Arachi ◽

Nazia Karsan ◽

Robin Ray ◽

Anthony C Pereira

Keyword(s):

Antiplatelet Therapy ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Current Evidence ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

Peripheral Ischaemia ◽

New Evidence ◽

Pfo Closure

Patent foramen ovale (PFO) is the most common anatomical cause of an interatrial shunt. It is usually asymptomatic but may cause paradoxical embolism, manifesting as stroke, myocardial infarction or visceral/peripheral ischaemia. PFO is a risk factor for stroke and may be associated with migraine with aura. New evidence suggests PFO closure reduces the risk of recurrent ischaemic stroke in a highly selected population of stroke survivors: those aged 60 years or younger with a cryptogenic stroke syndrome, a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation. They benefit from percutaneous PFO closure in addition to antiplatelet therapy, rather than antiplatelet therapy alone. Current evidence does not support PFO closure in the treatment of migraine.

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Patent Foramen Ovale Device Closure in a 27 Years Old Young Lady with Cryptogenic Ischaemic Stroke - First Case Report from Bangladesh

Cardiovascular Journal ◽

10.3329/cardio.v13i2.52978 ◽

2021 ◽

Vol 13 (2) ◽

pp. 227-234

Author(s):

AQM Reza ◽

Aparajita Karim ◽

Mahmood Hasan Khan ◽

Kazi Atiqur Rahman ◽

Md Aliuzzaman Joarder ◽

...

Keyword(s):

Ischaemic Stroke ◽

Patent Foramen Ovale ◽

Incidental Finding ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Foramen Ovale ◽

Coagulation Therapy ◽

First Case ◽

Treatment Paradigm ◽

Meta Analyses

A patent foramen ovale (PFO) is highly prevalent in patients with strokes of unknown cause or cryptogenic strokes (CSs). It has been remained an unsolved question as to whether a PFO should be closed or not to prevent recurrent strokes in patients diagnosed with cryptogenic stroke (CS). A paradoxical embolism through a PFO is pointed as a leading cause of CS, especially in younger patients with low risk factors for stroke. It also remains an unsolved matter on type of anti-coagulation therapy, which would be better for patients with CS and a PFO. In addition, surgical and transcutaneous closure of a PFO has been proposed for the secondary prevention of stroke in patients with CS with PFO. Several randomized controlled trials have been conducted in recent years to test whether a PFO closure gives a significant benefit in the management of CS. Many investigators believed that a PFO was an incidental finding in patients with CS. However, meta-analyses and more recent specific trials have eliminated several confounding factors and possible biases and have also emphasized the use of a shunt closure over medical therapy in patients with CS. Therefore, these latest studies can possibly change the treatment paradigm in the near future. We are reporting a case of cryptogenic ischaemic stroke in middle cerebral artery territory due to paradoxical embolism through a PFO which was successfully closed with a device solely by a Bangladeshi Consultant & his team first time in Bangladesh. Cardiovasc. j. 2021; 13(2): 227-234

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Abstract WP264: Frequency of Hypercoagulability in Patients With Embolic Stroke of Undetermined Source and Patent Foramen Ovale

Stroke ◽

10.1161/str.51.suppl_1.wp264 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Michael Liu ◽

Srikant Rangaraju ◽

Alexander Duncan ◽

Samir Belagaje ◽

Trina Belair ◽

...

Keyword(s):

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Embolic Stroke ◽

Composite Outcome ◽

Foramen Ovale ◽

Primary Mechanism ◽

Detailed Evaluation ◽

D Dimer

Introduction: Patent foramen ovale (PFO) is more commonly found in patients with cryptogenic stroke and paradoxical embolism is commonly assumed to be the primary mechanism. Our objective was to determine the frequency of hypercoagulability in cryptogenic stroke patients and PFO. Methods: Consecutive patients with embolic stroke of undetermined source (ESUS) seen at the Emory Clinic from January 1, 2017 to June 30, 2019 who underwent echocardiogram with bubble study and markers of coagulation and hemostatic activation (MOCHA) testing (serum d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) were included; abnormal MOCHA was defined as ≥ 2 elevated markers. Venous thromboembolism, malignancy, other defined hypercoagulable state, and the composite outcome were assessed at routine follow-up and compared across groups based on PFO status. Results: Of 172 patients (mean age 63 ± 16 years, 60% female), 40 (23%) had a PFO. Compared to the PFO- group, the PFO+ group was younger (p=<0.001), less likely to have hypertension (p<0.001) and diabetes (p=0.011), and had a higher ROPE score (p=0.007) (Table 1). There was no difference in the frequency of abnormal MOCHA between groups and the composite outcome was less frequent in PFO+ versus PFO- patients (p=0.017). In the subgroup of patients <60 years old, there was no difference in the frequency of abnormal MOCHA and the composite outcome. Conclusion: Hypercoagulability as measured by MOCHA was not associated with the presence of PFO in ESUS patients. Based on our results, ESUS patients should undergo a detailed evaluation for alternative causes of stroke other than paradoxical embolism.

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Abstract TMP13: Baseline DWMRI Characteristics In Patients With Cryptogenic Stroke And Patent Foramen Ovale: Results From The Closure I Trial

Stroke ◽

10.1161/str.44.suppl_1.atmp13 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Richard Jung ◽

Benny Kim ◽

Joseph Massaro ◽

Anthony J Furlan

Keyword(s):

Patent Foramen Ovale ◽

Cox Regression ◽

Recurrent Stroke ◽

Cryptogenic Stroke ◽

Patient Characteristics ◽

Paradoxical Embolism ◽

Foramen Ovale ◽

Anterior Circulation ◽

Significant Difference ◽

Multivariate Proportional Hazard

Background: Cryptogenic stroke may have several etiologies including paradoxical embolism through a patent foramen ovale (PFO). A cardiac source of embolism may be suggested by multiple infarcts, sometimes hemorrhagic, in different vascular distributions or a cortical wedge shaped infarct. We report the baseline diffusion weighted MRI (DWMRI) characteristics in patients with cryptogenic stroke and a patent foramen ovale (PFO) from the CLOSURE I trial. Methods: CLOSURE I compared device closure versus medical therapy for secondary prevention in patients with cryptogenic TIA or stroke and a PFO. Of 909 patients randomized, 562 patients demonstrated acute infarcts on baseline DWMRI and are included in this analysis. Multivariate proportional hazard Cox regression compared imaging subgroups with remaining randomized patients Results: Single infarcts were found in 62% of patients. Of these, 61% were anterior circulation, 30% posterior, and 8.5% were of uncertain territory. Of the anterior circulation infarcts, 40% were cortical, 36% subcortical, and 24% affected both the cortical and subcortical regions. Of the posterior circulation infarcts, 45% were thalamic or cerebellar. Of 562 patients, 18.5% had a single subcortical lesion <1.5cm in diameter and met the radiological definition of an acute lacunar infarct. Multiple infarcts were found in 38%. Infarcts in a single vascular territory were found in 23%, often in the anterior circulation (66%). Infarcts in multiple vascular territories were found in 15%. Hemorrhagic infarction was present in 9%. Adjusting for patient characteristics, no significant difference in 2 year rate of TIA, stroke or death was found compared to remaining randomized patients. Discussion: The specificity of infarct patterns for embolism in patients with cryptogenic stroke and a PFO is uncertain. We found no significant relationship between lacunar or subcortical infarction and the risk of recurrent TIA or stroke. Baseline infarct patterns on DWMRI in patients with cryptogenic stroke and PFO may not be useful in predicting recurrent stroke risk or determining best prevention therapy.

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