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Patent foramen ovale

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In the fetal heart, the foramen ovale allows blood to enter the left atrium from the right atrium. 

It is one of two fetal cardiac shunts, the other being the ductus arteriosus, which allows blood that still escapes to the right ventricle to bypass the pulmonary circulation.

Allows right to left intracardiac shunting.

In most individuals, the foramen ovale closes at birth., and it later forms the fossa ovalis.

The foramen ovale forms in the late fourth week of gestation, as a small passageway between the septum secundum and the ostium secundum. 

Initially the atria are separated from one another by the septum primum except for a small opening below the septum, the ostium primum. 

As the septum primum grows, the ostium primum narrows and eventually closes. 

Bloodflow from the inferior vena cava wears down a portion of the septum primum, forming the ostium secundum.

The ostium secundum provides communication between the atria after the ostium primum closes completely. 

Subsequently, a second wall of tissue, the septum secundum, grows over the ostium secundum in the right atrium. 

Blood then passes from the right to left atrium only by way of a small passageway in the septum secundum and then through the ostium secundum. 

This passageway is called the foramen ovale.

Occurs in about one fourth of the general population.

Is present in more than 25% of the adult population at autopsy.

The foramen ovale normally closes at birth. 

No cause is established for a foramen ovale to remain open instead of closing naturally, but heredity and genetics may play a role.

At birth, when the lungs become functional, the pulmonary vascular pressure decreases and the left atrial pressure exceeds that of the right, which forces the septum primum against the septum secundum, functionally closing the foramen ovale. 

In time the septa eventually fuse, leaving a remnant of the foramen ovale, the fossa ovalis.

The fetus receives oxygen not from its lungs, but from the mother’s oxygen-rich blood via the placenta. 

Oxygenated blood from the placenta travels through the umbilical cord to the right atrium of the fetal heart. 

As the fetal lungs are non-functional.

The blood bypasses them through two cardiac shunts.

The first is the foramen ovale which shunts blood from the right atrium to the left atrium. 

The second is the ductus arteriosus which shunts blood from the pulmonary artery to the descending aorta.

In about 25% of adults the foramen ovale does not close completely, but remains as a small patent foramen ovale.

In most of these individuals, the PFO causes no problems and remains undetected throughout life.

PFO has a role in paradoxical embolism that may lead to a stroke or transient ischemic attack. 

Transesophageal echocardiography (TEE) is considered the most accurate investigation to demonstrate a patent foramen ovale. 

A TTE with bubble study is performed by injecting agitated saline into a vein while a patient performs a Valsalva maneuver to increase right atrial pressure.

PFO is diagnosed by visualizing micro bubbles in the left atrium within three cardiac cycles, indicating a right to left across the atrial septum.

A TEE with bubble study has a sensitivity of 71% and a specificity of 99% for identifying a PFO but is considered inadequate to rule out a PFO.

Transesophageal echocardiography involves the insertion of an ultrasound probe in the esophagus, and it’s typically performed with conscious sedation and can identify PFO with a sensitivity of 89% and the specificity of 91%.

A patent foramen ovale may also be an incidental finding.

Generally asymptomatic.

Can be a source of paroxidal embolism.

Can be associated with stroke.

May comprise 10% of ischemic strokes and young a middle-aged adults aged 18 to 60 years.

Prevalence decreases with advancing age.

More frequent in young patients with cryptogenic strokes than in the general population.

It is presumed that cryptogenic strokes are due to paradoxical embolisms that result due to a passage of a venous thrombus across a patent foremen ovale to enter the systemic circulation

Prevalence of 34% in first 3 decades of life and down to 20% by the ninth decade.

Patent foramen ovale seen in 15-35% of people, but associated paradoxical embolism is rare.

Associated with cryptogenic strokes.

Associated with an increased risk of migraines, particular in those with a sizable shunt fraction.

Research suggests  that a proportion of cases of migraine may be caused by PFO, and closure of a PFO can reduce symptoms in certain cases.

Percutaneous PFO closure is performed by insertion of a closure device via a catheter into the right atrium via the femoral vein.

The device is deployed across the PFO, where it covers the PFO and becomes integrated into the cardiac tissue overtime.

This remains controversial; 20% of the general population has a PFO, which for the most part, is asymptomatic. 

The risk of paradoxical embolism (RoPE score) include six clinical characteristics – age, history of stroke, or TIA, diabetes, hypertension, smoking, cortical infarct on imaging, and ranges from 0 to 10.

Among patients with the lowest RoPE score category, the prevalence of PFO was 23%, similar to the general population,bsuggesting a PFO attributable fraction near zero.

The prevalence of PFO and cryptogenic stroke and a ROPE score of 9-10  is 77% suggesting a PFO attributable fraction of approximately 90% to these patients while among patients with the lowest ROPE score the prevalence of PFO is 23% similar to the general population.

About 20% of the female population has migraines, and the placebo effect in migraine typically averages around 40%.

The high frequency of these facts make finding statistically significant relationships between PFO and migraine difficult.

In a large randomized controlled trial, migraine headache cessation was not more prevalent in the group of migraine patients who underwent closure of their PFOs.

Present in 35-45% of patients with cryptogenic strokes compare with 25% in the general population.

Associated with strokes at all ages.

Systemic embolic events occur in increased frequency among patients with a patent foramen ovale, even in the absence of right to left shunting.

Can cause ischemic stroke by paradoxical embolic means.

Incidence of cryptogenic strokes without evidence of cardiac or cerebrovascular disease is approximately 200,000 per year

From 70-90,000 of cryptogenic strokes have a patent foramen ovale.

Size of shunt is correlated with risk of stroke.

Risk of stroke increased in patients with pulmonary embolism and a patent foramen ovale.

Increased in risk in patients with cryptogenic strokes.

The mechanism by which a PFO may play a role in stroke is called paradoxical embolism: a blood clot from the venous circulatory system is able to pass from the right atrium directly into the left atrium via the PFO, rather than being filtered by the lungs, and thereupon into systemic circulation toward the brain.

PFO is common in patients with an atrial septal aneurysm (ASA), a much rarer condition, which is also linked to cryptogenic stroke.

While PFO is present in 25% in the general population, the probability of someone having a PFO increases to about 40 to 50% in those who have had a cryptogenic stroke.

Increased age associated with increased risk of paradoxical embolism.

Diameter of the lesion increases with age.

Most PFO‘s have a small diameter 1 to 19 mm and do not cause hemodynamically significant shunting of blood.

If PFO is large enough to permit emboli from a venous rhombus to bypass filtration in the pulmonary vascular it can  access the systemic circulation.

This paradoxical embolism can cause symptomatic strokes by occluding a branch in the cerebral arterial circulation

Can lead to ischemic limb infarction, visceral infarction, myocardial infarction, TIAs, and pulmonary embolism.

In the presence of aspirin or warfarin therapy associated with increase risk of adverse events in older but, but not in younger individuals.

Lower prevalence of patent foramen ovale in older individuals than in younger patients with cryptogenic strokes, as alternative causes more likely in older patients.

The concomitant presence of an atrial septal aneurysm with a patent foramen ovale increases the risk of paradoxical embolism and stroke.

Closure of a patent foramen ovale in patients with ischemic stroke may reduce risk of recurrent stroke compared with medical therapy alone (Schuchlemz HW et al, Wahl A et al).

Catheter closure of patent foramen may be inferior management to medical therapy according to meta analyses.

In a multicenter study of patients with patent foramen ovale and ischemic stroke, TIA, or a peripheral thromboembolic event were randomly treated with the Amplatzer PFO Occluder or medical therapy: no significant reduction in risk of recurrent embolic events or death occurred as compared to medical therapy (Meier B et al).

Three randomized clinical trials comparing patent foremen ovale closure with medical therapy failed to show a significant advantage of patent foremen ovale closure.

Other studies should significant reduction in stroke incidence when comparing patent ovale foramen closure with antiplatelet therapy with incidences of zero versus 4.9% and 1.4 versus .4%.
Presently there is no current known difference in stroke incidence between antiplatelet and anticoagulation strategies in patients who have had a stroke and not having patent foramen closure.

Approximately 50% of patients 60 years or younger with embolism stroke of undetermined source i.e. cryptogenic stroke, have a PFO compared with 25% of the general population.

However, studies show that patients with a patent foremen ovale closure who have in addition atrial septal aneurysm have a significant decrease in cryptogenic strokes, and without an aneurysm of the atrial septum, patent foramen ovale closure is not indicated.

In the CLOSE study 663 patients with patent foramen ovale and large interatrial shunts are atrial septal aneurysm were randomized to a patent foramen ovale device closure or medical therapy and followed for a mean of 5.3 years: significantly fewer strokes occurred in the patent foramen ovale closed group.

In the Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed TIA in Patients with foramen ovale trial. 664 patients

With patent foramen ovale, of whom 81% had moderate to large interatrial shunts were randomized to patent foramen ovale closure plus antiplatelet therapy or antiplatelet therapy alone and followed for a mean of 3.2 years: there were significantly fewer clinical ischemic strokes in the patent foramen ovale closure group.

Meta-analysis have shown that closure is associated with a lower rate of recurrent ischemic stroke, however absolute risk of stroke recurrence remain very low for some patients with medical therapy and device closure has been associated with risk for adverse effects.
Percutaneous PFO closure substantially reduces the risk of stroke, recurrence in well selected patients younger than 60 years after cryptogenic stroke.
Even after PFO closure patients with cryptogenic stroke and PFO have a highest stroke risk of four year follow up have a higher stroke risk compared with general population: recurrence is associated with cardiovascular risk factors, such as age, hypertension, diabetes, dyslipidemia, and smoking status underscoring the importance of managing vascular risk factors.
In the Randomized Evaluation of Recurrent Stroke compared patent foramen closure to established current standard of care treatment trial, 980 patients with patent foramen ovale, of whom 49% had a substantial interatrial shunt and 36% had an atrial septal aneurysm, were randomized to patent foramen ovale device closure or medical therapy: at a median of 2.1 years there was no significant benefit to patent foramen ovale closure, at 5.9 years it was significantly fewer strokes in the closure group.
The rate of periprocedural complications in patent foramen ovale closure is increased incidence of self-limited atrial fibrillation in the first six months after closure.
A causal classification system can randomize patients into sub groups, those who may benefit from PFO closure from those unlikely to receive benefit.
PFO closure is generally safe but serious adverse effects may occur and include atrial fibrillation/flutter, 3.7%, vascular complications of hemorrhage/hematoma and vascular complications required surgical repair at 3%, hematoma/hemorrhage 2.7%, cardiac tamponade/perforation 0.5%, pneumothorax/hemothorax 0.1%, and death 0.3%.
The number of patients experiencing any serious adverse event is similar in PFO closure group and medical therapy group (28.7% vs 26.4%).
The relative reduction in the rate of recurrent stroke is significantly greater with patients with a lower risk of paradoxical embolus as the cause.
The potential benefits of PFO closure in patients older than 60 years is uncertain.
PFO closure may be reasonable for patient’s age 60 to 65 years who have high risk PFO features such as a large shunt and an atrial septal aneurysm, despite RoPE score less than seven.
The reduction and risk of recurrent stroke of 40% in those with RoPE scores less than seven and 80% in those with RoPE scores seven or greater.
PASCAL score (the PFO – Associated Stroke Causal Likelihood) includes the RoPE score and echocardiographic findings with high risk anatomical features defined as a large shunt and/or atrial septal aneurysm.
The PASCAL score is used to help determine the benefit of PFO closure.
Comparing an anticoagulant with anti-platelet therapies in patients with PFO associated stroke finds that anticoagulation with oral anticoagulant is associated with a lower risk of recurrent ischemic stroke (3.2%) compared with anti-platelet therapy with aspirin (5.5%) in metaanalysis: in randomized trials, the comparative effectiveness of PFO closure versus anticoagulation alone remains uncertain.
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