Patent foramen ovale-associated stroke: mechanisms, diagnosis, risk stratification, and management

Q: What is the clinical evidence from this study?

Study design: Review. Population: Patent foramen ovale-associated cryptogenic stroke. Intervention: Patent foramen ovale (PFO) closure and diagnostic/risk stratification strategies vs. Medical therapy alone. Primary outcome: Recurrent stroke.

Q: What does this research mean for the field?

Establishing causality and recurrence risk in PFO-associated cryptogenic stroke requires evaluating high-risk anatomical features and non-paradoxical mechanisms such as in situ thrombosis to guide patient selection for closure. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Luyi Zhang; Zihao Li; Yanxing Zhang

doi:10.3389/fneur.2026.1889405

November 2, 2026Frontiers in NeurologyOpen Access

Patent foramen ovale-associated stroke: mechanisms, diagnosis, risk stratification, and management

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Key result

PFO closure reduces recurrent stroke risk compared with medical therapy alone after cryptogenic stroke.

Why the study?

Identifying the causal relationship between patent foramen ovale and cryptogenic stroke and assessing the risk of stroke recurrence remain clinical challenges.

How do multimodal diagnostic tools, risk stratification strategies, and PFO closure impact the diagnosis and management of PFO-associated cryptogenic stroke?

Key Points

To review the pathophysiological mechanisms, diagnostic pathways, biomarkers, and risk stratification methods for patent foramen ovale-associated stroke, while evaluating indications for transcatheter closure.
Narrative review of peer-reviewed literature retrieved from PubMed through February 2026, including clinical trials, cohort studies, and meta-analyses.
Patent foramen ovale is identified in 40% to 56% of patients with cryptogenic stroke, compared to approximately 25% of healthy individuals.
Paradoxical embolism is the primary established mechanism, but in situ thrombosis serves as an independent risk factor (OR 3.29, 95% CI 1.49–7.26, p=0.003), often interacting synergistically with atrial septal aneurysms.
PFO closure reduces recurrent stroke risk relative to medical therapy alone, though evidence remains limited regarding optimal post-closure medication regimens and efficacy in individuals older than 60 years.

Structured PICO

How do multimodal diagnostic tools, risk stratification strategies, and PFO closure impact the diagnosis and management of PFO-associated cryptogenic stroke?

P

Population

Patients with patent foramen ovale (PFO)-associated cryptogenic stroke

I

Intervention

Patent foramen ovale (PFO) closure and multimodal diagnostic/risk stratification evaluations (including c-TEE, c-TTE, c-TCD, CCT, CMRI, and OCT)

C

Comparator

Medical therapy alone or alternative diagnostic modalities

O

Outcome

Recurrent stroke and diagnostic accuracy for PFO and right-to-left shunting

This review synthesizes the pathophysiological mechanisms (including paradoxical embolism, in situ thrombosis, and atrial cardiopathy) and diagnostic modalities for PFO-associated stroke to guide patient selection for PFO closure.

Limitations

Exclusion of non-English publications, case reports, and letters
Lack of causal validation in observational studies of left atrial dysfunction and atrial arrhythmias
Further research is needed on post-closure medical management and PFO closure in patients over 60 years of age
Literature search excluded non-English publications, case reports, and letters
Observational nature of underlying studies on left atrial dysfunction and in situ thrombosis requires further validation in larger cohorts
Evidence gaps remain regarding post-closure medical management and PFO closure in patients over 60 years of age

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Answers are grounded in this paper and cite their sources.

Implication

Informs PFO closure decisions in cryptogenic stroke; leaves open optimal regimens and efficacy beyond age 60.

Abstract

Patent foramen ovale (PFO) is present in some people, and PFO may lead to cryptogenic stroke. How to identify the causal relationship between PFO and cryptogenic stroke and how to assess the risk of stroke recurrence remain clinical challenges. We reviewed the related mechanisms, diagnosis, relevant biomarkers and the risk assessment of PFO-associated stroke. We also discussed recent advances in PFO closure and its potential indications. Further researches are needed on post-closure medical management and the use of PFO closure in patients over 60 years of age.

Discussion

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Cite This Study

Zhang et al. (2026) conducted a review in Patent foramen ovale-associated cryptogenic stroke. Patent foramen ovale (PFO) closure and diagnostic/risk stratification strategies vs. Medical therapy alone was evaluated on Recurrent stroke. Patent foramen ovale is detected in 40% to 56% of patients with cryptogenic stroke, and PFO closure reduces the risk of recurrent stroke compared with medical therapy alone.

synapsesocial.com/papers/6aea772189a8acbed9c87aaf https://doi.org/10.3389/fneur.2026.1889405

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Patent foramen ovale-associated stroke: mechanisms, diagnosis, risk stratification, and management

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Patent foramen ovale-associated stroke: mechanisms, diagnosis, risk stratification, and management

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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