Advances in the management of cardioembolic stroke associated with patent foramen ovale

Abstract

Patent foramen ovale (PFO) describes a valve in the interatrial septum that permits shunting of blood or thrombotic material between the atria. PFOs are present in approximately 25% of the healthy population and are not associated with any pathology in the vast majority of cases. However, comparisons between patients with stroke and healthy controls suggest that PFOs may be causative of stroke in certain patients whose stroke is otherwise cryptogenic. Options for the diagnosis of PFO include transthoracic echocardiography, transesophageal echocardiography, and transcranial Doppler ultrasonography. PFOs associated with an interatrial septal aneurysm seem to be more strongly linked to risk of recurrent stroke. Therapeutic options for secondary stroke prevention in the setting of a PFO include antiplatelet therapy, anticoagulation, and percutaneous device closure. Recent randomized clinical trials suggest that percutaneous closure reduces the subsequent risk of stroke in appropriately selected patients, with a large relative benefit but small absolute benefit. Referral for percutaneous PFO closure should therefore be considered in certain patients after a multidisciplinary, patient centered discussion. Areas for future study include structural biomarkers to aid in determining the role of PFO closure in older people with possible PFO associated stroke, the role of direct oral anticoagulants, and very long term outcomes after device closure.

Transcatheter Patent Foramen Ovale Closure in Stroke Patients with Thrombophilia: Current Status and Future Perspectives

“…The presence of a PFO has been shown to be a common finding in the general population, with a prevalence between 20% and 34%. 4 PFO is detected more frequently in young adults with an ischemic stroke of undetermined etiology (54% to 56%) compared to non-stroke controls (10% to 18%). 14 A meta-analysis including 23 case-control studies in patients younger than 55 years showed a strong association between the presence of a PFO and cryptogenic stroke, the nowadays referred as "PFO-associated stroke," 15 compared to stroke of known etiology (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3 to 7.8).…”

“…2 The classification, prevalence, and estimated risk, alongside their inherited or acquired forms for the types of thrombophilias related to a PFO-associated stroke and their supporting evidence are shown in Table 1. [2][3][4]10,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Role of patent foramen ovale in systemic thromboembolism…”

“…Two mechanisms have been proposed to explain the role PFO in systemic embolism: (1) paradoxical embolism, which implies the passage of a right-sided venous thrombus to the left circulation through the PFO, specially during transient or persistent elevations on right-heart pressures which would allow to the passage of blood (or thrombus) from the right atrium to the left atrium, and (2) in situ PFO thrombus formation, which can lead to embolization to the left circulation. 4,29 Both mechanisms can be enhanced in the setting of thrombophilia, which may increase by several times the risk of thrombus formation in the venous system or in the PFO. Both circumstances have been studied and further characterized, leading to the identification of high-risk features for PFO including a large PFO (maximum separation of the septum primum from the secundum >2 mm), long tunnel (>10 mm), atrial septal aneurysm (hypermobility of the septum with >10 mm excursion), strongly positive bubble study, and prominent Eustachian valve.…”

“…The prevalence of thrombophilia in the general population ranges between 0.1% and 20%, 2,3 and the prevalence of PFO from 20% to 34%. 4 Interestingly, the prevalence of both conditions is higher in stroke patients compared to the general population, and both have been associated with a higher risk of cerebrovascular events. 5 Due to scarce and inconsistent clinical evidence, 6 and to the exclusion of patients with thrombophilia from most PFO closure randomized clinical trials, current guidelines regarding the management of PFO-stroke patients failed to make strong recommendations on transcatheter closure in such patients along with the lack of indication for thrombophilia screening in this setting.…”

“…This has been extensively demonstrated in large randomized clinical trials which excluded a significant proportion of patients who could have benefited from percutaneous PFO closure due to coexisting potential confounders such as additional thromboembolic risk factors, namely thrombophilia. The prevalence of thrombophilia in the general population ranges between 0.1% and 20% [ 2 , 3 ], and the prevalence of PFO from 20% to 34% [ 4 ]. Interestingly, the prevalence of both conditions is higher in stroke patients compared to the general population, and both have been associated with a higher risk of cerebrovascular events [ 5 ].…”