Abstract Body (Do not enter title and authors here):

Background: Patent foramen ovale (PFO) is a recognized contributor to embolic stroke, especially in hypercoagulable states (HCSs). However, patients with HCSs, including malignancy, were excluded from major PFO closure trials, creating a significant evidence gap.

Objectives: This narrative review examines the role of PFO closure in secondary stroke prevention among patients with HCSs, including malignancy. We highlight key studies and current evidence in this understudied population.

Methods: A systematic search of PubMed was conducted using pertinent MeSH terms. Due to limited data, a narrative synthesis of the literature was performed.

Case Presentation and Narrative Review of Literature:
A 43-year-old lady with a history of metastatic breast cancer and recent bilateral pulmonary emboli on anticoagulation (AC), presented with expressive aphasia. MRI brain confirmed a Broca-area infarct. Biopsy of an expansile pelvic mass yielded a diagnosis of ovarian mucinous cystadenocarcinoma. TEE demonstrated a PFO; an embolic stroke driven by hypercoagulability of malignancy was diagnosed. PFO closure was offered for secondary stroke prevention after risk-benefit discussion, as opposed to AC alone.
While early trials (CLOSURE I, PC) showed no benefit of closure, subsequent studies (RESPECT, REDUCE, DEFENSE-PFO) favored it in selected patients, but notably, these trials excluded patients with HCSs and malignancy. The benefit of PFO closure in this population thus comes largely from observational data. Abrahamyan et al. found that PFO closure could be safely offered in patients with thrombophilia to prevent recurrent stroke. Liu et al., in their prospective study, noted that among patients with cryptogenic stroke and thrombophilia, PFO closure lowered the risk of recurrence. Similarly, a retrospective study from Greece found benefit from PFO closure in this population. Buber et al. found that among patients with HCSs and stroke, PFO closure offered a five-fold risk reduction from future CVA/TIA. The Society for Cardiovascular Angiography and Interventions (SCAI) guidelines recommend PFO closure in patients with thrombophilia for secondary stroke prevention (conditional recommendation- low certainty of evidence).

Conclusions: Data on PFO closure for secondary stroke prevention in HCSs and malignancy are scant, necessitating individualized decision making. Current evidence supports PFO closure, but future studies are needed specifically in this vulnerable population.