Long-term cerebrovascular outcomes of patients undergoing percutaneous patent foramen ovale closure in observational studies: a systematic review and meta-analysis

Objectives: Patent foramen ovale (PFO) closure is recommended for patients who experience a cryptogenic stroke attributable to PFO. Although few randomized control trials (RCTs) have captured long-term effectiveness of PFO closure, observational data has been abundant. This is the first systematic review of observational studies determining incidence of long-term adverse outcomes in adults who underwent transcatheter PFO closure, with comparisons to findings from RCTs.

Methods: Medline, Cochrane, and Embase databases were searched from inception to October 2023. Only observational studies with ≥4 years of mean or median follow-up were included. A meta-analysis was conducted to calculate the incidence of recurrent stroke after PFO closure.

Results: After reviewing 2,432 records, 13 prospective and 12 retrospective cohort studies were included. Average follow-up lengths ranged from 4 to 12.3 years, and sample sizes from 75 to 1,533 participants. The average age ranged between 43.5-63.0, and 24.0-72.8% patients had an atrial septal aneurysm. The incidence of stroke was 0.34 per 100 person-years (I² = 67%). This was similar to rates from four RCTs that were used for comparison (0.35 per 100 person-years, I²= 51%). There was a significant improvement in heterogeneity once the study with one of the largest follow-up was removed.

Conclusions: Real-world PFO closure studies with long-term follow-up report similar outcomes as RCTs which is important considering the exclusion of several important populations from trials. Future observational studies should include more rigorous reporting of follow-up strategies and explore different long-term adverse outcomes.