Paradoxical Embolus from Patent Foramen Ovale Resulting in Transient Vision Loss
Save as PDFABSTRACT
BACKGROUND
A patent foramen ovale (PFO) is a small, flap-like opening between the right and left atrium of the heart.1 It is the most common heart abnormality of fetal origin – present in approximately 25% of the worldwide adult population.2 Historically, PFOs are associated with increased stroke risk due to the paradoxical embolism of venous thrombi that shunt through the PFO directly to the oxygenated left atrium. Transthoracic echocardiography, transesophageal echocardiography and transcranial doppler are all methods used in detection of PFOs. Although typically untreated when asymptomatic, treatment with antiplatelet or anticoagulation therapy, or even closure, is indicated in circumstances of low oxygen levels, blood clots, and strokes.2
CASE REPORT
A 48-year-old African American female presented with a history of two incidents of transient vision loss of the left eye. In both instances, she stated she experienced a “darkness” over the left eye that lasted about 15 minutes before self-resolution. She would alternate closure of each eye during the incidences to confirm the visual change was only occurring in the left eye. Following both incidents, she reported a transient tingling sensation on the left side of her body. She had an established history of mid-frontal headaches on the left side of her head but denied scalp tenderness or jaw claudication. Pertinent history included prior deep vein thrombosis and pulmonary embolism, for which the patient was prescribed Eliquis. Ophthalmic examination revealed normal ocular health in both eyes. Through consultation with cardiology, it was determined her transient vision loss was a result of paradoxical embolism via PFO, and the patient was scheduled for PFO closure surgery.
CONCLUSION
A plethora of etiologies can ultimately lead to the manifestation of unilateral vision loss. It is important therefore to understand the different ways in which it may occur. This case highlights the importance of understanding ocular symptoms in the setting of cardiac pathology. Careful consideration of the patient’s history led to a presumed etiology for her symptoms, appropriate work up, and thus intervention in order to prevent recurrent episodes.
Keywords: deep vein thrombosis (DVT), transient ischemic attack, stroke, unilateral vision loss, Patent Foramen Ovale (PFO), paradoxical embolism
INTRODUCTION
A patent foramen ovale (PFO) is a small, flap-like opening between the right and left atrium of the heart. During fetal development, it allows oxygenated blood to flow within fetal circulation, circumventing the nonfunctional fetal lungs. However, if left open after birth, a left-right shunt in the atrium can develop. Subsequently, this can lead to a crossing of the deoxygenated blood of the right atrium with the oxygenated blood of the left if it remains open after birth.1
Within the fourth week of embryonic development, the septum primum develops in the middle of the common atrium of the fetal heart. Eventually, the tissue of the superior portion of the septum primum is reabsorbed to form the septum secundum. The superior limb of the septum secundum overlaps the thin-walled septum premium to form a valve-like structure known as the foramen ovale. Typically, this will close after birth due to an increase in the left atrial pressure above the right atrial pressure.1
PFOs are the most common fetal heart abnormality, present in approximately 25% of the world population.2 This prevalence is based on autopsy and transesophageal echocardiography (TEE) studies, since it can remain hemodynamically insignificant in most cases.3 PFOs may be discovered incidentally in asymptomatic patients who may live their entire life without closure. Conversely, patients can experience mild to severe symptoms which includes right heart failure, stroke and severe pulmonary vascular disease like Eisenmenger syndrome.4
Typically, PFOs may be simply monitored by a cardiologist, as the stroke risk is minimal when patients are asymptomatic. If symptomatic, the risk of low oxygen levels, blood clots, or strokes rises and treatment is considered. This is often first by antiplatelet or anticoagulation therapy, then by surgical closure as indicated.5 Historically, PFOs have been associated with increased stroke risk due to the paradoxical embolism of venous thrombi that shunt through the PFO directly to the oxygenated left atrium. 6 The following case report highlights how a patient’s amaurosis ultimately led to diagnosis and treatment of a PFO.
CASE REPORT
A 48-year-old African American female presented to the clinic with a history of two episodes of transient vision loss of the left eye, occurring the night before and the morning of her exam. In both instances, she stated she experienced a “darkness” over the left eye for about 15 minutes followed by spontaneous self-resolution. She would alternate closure of each of her eyes during the incidences to confirm the visual change was only occurring in the left eye. Following both incidents, she reported a transient tingling sensation on the left side of her body. The patient had an established history of mid-frontal headaches on the left side of her head but denied scalp tenderness or jaw claudication. Pertinent history included prior deep vein thrombosis and pulmonary embolism, for which she was prescribed Eliquis. She also was previously established to have obesity, obstructive sleep apnea with use of continuous positive airway pressure machine, depression and post-traumatic stress disorder. She was also taking birth control at the time in the form of a hormonal IUD (intrauterine device).
Vision was correctable to 20/20 in each eye with full confrontational and 30-2 Humphrey visual fields and normal extraocular motilities. Pupil testing was unremarkable with full color vision in both eyes and an unremarkable red cap desaturation test. Hertel exophthalmometry was unremarkable and equal between both eyes at 21 mm. Pressures were normal and the anterior segment was unremarkable in both eyes. The right optic nerve showed 0.25r cupping with pink and distinct borders, while the left eye showed 0.20r cupping with pink and distinct borders. Posterior pole and peripheral retinal examination was unremarkable in both eyes.
Following the exam, she was sent to the emergency department for a full systemic work up given extensive differentials for amaurosis fugax. Guidance was given to rule out migraines. Labs were ordered and urgent neurology and cardiology consultations were placed.
Her lab work revealed only slightly elevated ESR and CRP, with no significant plaque or stenosis of internal or external carotid arteries present. She showed a mildly positive ANA, but no evidence of lupus anti-coagulant. The patient was seen by the rheumatology service who determined that her ANA results were not clinically relevant. Protein C antigen, Protein S, prothrombin and Factor V Leiden labs were negative. Brain MRI ruled out space-occupying lesions and acute cerebrovascular attack. Due to elevated inflammatory markers, vasculitis then needed to be ruled out, leading to a follow-up carotid sonogram, which was unremarkable.
The cardiology service ran a transthoracic echocardiogram which showed overall normal systolic function with no evidence of pulmonary hypertension. However, bubble study revealed a patent foramen ovale with right-to-left passage of saline contrast with release on valsalva. According to cardiology, the transient vision loss was likely from a paradoxical embolus from PFO. She was referred for surgical PFO closure and placed on a treatment regimen including aspirin, statin, and enoxaparin.
DISCUSSION
Systematic review of percutaneous PFO closure has shown the procedure to be safe and effective in patients with previous stroke, transient ischemic attacks and other complex PFO-associated clinical conditions. Long-term prevention of recurrent cerebrovascular events, reduction in migraine symptoms and improvement in quality of life are all factors positively associated with closure.7
Health-related quality of life is crucial when considering PFO closure. When comparing outcomes for patients receiving PFO closure vs those who did not, after a 12-month period, those patients who had PFO closure had significantly higher physical vitality, general health, mental health and social functioning have been reported.8 This also reflected in better anxiety and depression scores.8 In addition, systematic reviews and meta-analyses of randomized trials on PFO closure have shown it to be a more cost-effective solution for long-term secondary prevention of stroke.9
Determining which patients are appropriate for PFO closure requires assessment of each patient’s individual symptoms and clinical presentation. The current dogma remains nuanced. The guidelines according to the Society for Cardiovascular Angiography and Interventions (SCAI) state PFO closure consideration should be highly individualized in the context of a multidisciplinary approach. They state that PFO closure can be helpful in the prevention of recurrent stroke, migraine headaches and decompression illness.10 In patients with a non-lacunar ischemic stroke of undetermined cause and a PFO, recommendations for PFO closure versus medical management should be made jointly by the patient, a cardiologist, and a neurologist, accounting for the probability of a causal role for the PFO.
PFO is present in a considerable number of patients with aura migraines.7 The recommendation for PFO closure in response to migraines has been highly debated. The general theorem proposed is that vasoconstriction and activation of clotting factors play a role in migraine development, suggesting focal ischemia as a concurrent outcome of migraine attacks. Studies on PFO and migraines, however, have generally shown mixed results.
One case report relevant to this case involved a 31-year-old woman who suffered from a stroke with subsequent symptoms of sudden right sided weakness, dysarthria and sudden painless vision loss of the left eye. Before discovery of a PFO with substantial right-to-left shunt, her only risk factor for stroke was oral contraceptive use. Following her onset of stroke symptoms, a trans-catheter closure of the PFO was indicated.11
Several factors are considered when classifying a PFO as “high risk” for occurrence of stroke. These include a history of atrial septal aneurysm at least 15 mm beyond the level surface of the atrial septum and hypermobility (phasic septal excursion into either atrium ≥10 mm, or PFO size ≥2 mm). The most important of these factors appears to be size; however, there has been large variability among studies. It should be noted that at this time, large scale randomized controlled trials are necessary to more strongly determine the predictive values of such factors of stroke incidence and recurrence.12
Approximately 30% of ischemic strokes have no identifiable cause and are labeled as cryptogenic. Of these, PFO may play a significant factor. Prior systematic review and meta-analysis of prior randomized controlled trials displayed PFO closure reduced risk of cryptogenic stroke compared with medical therapy alone.13 PFO closure is generally considered a therapeutic option that should be offered to adults with cryptogenic stroke. Of note, patients with large shunts, those ≤45 years old, and male patients are more likely to benefit from PFO closure.13 Specifically, in the case of patients with PFOs with recent cryptogenic ischemic stroke with concurrent high-risk characteristics, the recurrence of stroke has been seen to be significantly lower with a combination of PFO closure alongside medical therapy.12 Fortunately, the patient in this case suffered strictly from pulmonary embolism, with no history of stroke.
Young adults with transient vision loss should be carefully examined for underlying pathology. For example, associated systemic diseases have been seen in 40-67% of central retinal vein occlusions (CRVOs) in young adults.14 Underlying systemic conditions include hereditary thrombophilias, blood dyscrasias, autoimmune disease, HIV, and pregnancy. Medical contributions include oral contraceptives, hormone therapy and diuretics. In some cases, even dehydration has been shown to cause monocular vision loss.14 Assessment following monocular vision loss should include blood pressure, hemoglobin A1C, complete blood cell count, lipid profile and erythrocyte sedimentation rate.14 One prospective cohort study on the prevalence of systemic complications in young (<45 years) adults with monocular vision loss found that of twenty participants, one had fibromuscular dysplasia and two had PFOs. Of note, 16 of the 20 participants were women. This suggests cardiac and neuroimaging workup are both necessary in cases of transient vision loss of young adults.15 In young adults with no evidence of vasculopathy, there may have been vision loss due to reversible vasospasm of retinal arteries, also known as a “retinal migraine.” This, however, exists as a diagnosis of exclusion.16
Following our patient’s surgical PFO repair and treatment initiation, she denied further symptoms of TIA at subsequent eye exams. She was determined to be low risk for cerebrovascular or transient ischemic attacks. She did, however, report a five-minute episode one month later in which she experienced a white “cloud” over her left eye. Following that episode, the ophthalmic examination, including FA and repeat DFE were unremarkable. Due to her history of extensive workup, the episode was unlikely to represent amaurosis and was instead diagnosed as a retinal migraine and stood as an incident separate from her prior episodes of amaurosis. The International Headache Society (IHS) lays out the definition of a retinal migraine as attacks of fully reversible monocular visual disturbance associated with migraine headache and a normal neuro-ophthalmic examination between attacks.17 While both symptoms are of concern, positive (“white cloud”) and negative (darkness) scotomas have crucial differentiating factors in their etiology. Negative scotomas encompass temporary or permanent vision loss, typically arising from retinal or optic nerve ischemia.18 Conversely, positive scotomas are commonly present as auras in different variations of migraines.19 As mentioned before, PFOs can be associated with migraines; however, closure has been shown to significantly reduce symptoms. Systemic work-up alongside an unremarkable ocular health exam ultimately led to our diagnosis of retinal migraine. Following her PFO closure and medication regimen, her blood labs and imaging were stable. There was no indication of stroke or comorbid etiology, and her symptoms fully self-resolved. This “white cloud” never returned after the initial presentation.
CONCLUSION
Transient vision loss is often a crucial indicator of impending cerebrovascular accidents but can also signal severe ocular or neurological pathology. An extensive work-up for transient vision loss should not be limited to one of those three factors. A PFO is not necessarily a top differential for transient vision loss, but it can be determined through a comprehensive workup. Considering the benefits of stroke prevention and minimization of symptoms, closure of a PFO may be considered when TIA symptoms are present. In this case, the incidence of transient vision loss coupled with other signs and symptoms of ischemia (transient tingling sensation of her left side) led to the diagnosis of PFO and development of a a management plan for PFO closure in a symptomatic patient. It highlights how clinicians should take a comprehensive approach with stroke symptoms and understand the correct referrals and treatments necessary.
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Dr. Marlin John received his Optometric degree from SUNY College of Optometry and completed residency training in ocular disease and vision rehabilitation at Northport VA Medical Center. He Specializes in vision rehabilitation at Jamaica Plain and Brockton VA Medical Centers.
Caryn Herman, OD, FAAO is chief of optometry at the Northport VA Medical Center.
