Effect of Patent Foramen Ovale (PFO) Closure After Stroke on Circulatory Biomarkers.

2021 
OBJECTIVE To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers. METHODS Consecutive PFO-related stroke patients were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood, pre and post PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort. RESULTS PFO stroke patients (n=254) were recruited and followed up to four years (median: 2.01; IQR: 0.77∼2.54). Metabolite profiling in discovery cohort (n=12) identified homocysteine as the most significantly decreased factor in intra-cardiac plasma after PFO closure (FDR=0.001). This was confirmed in validation cohort (n=181), where intra-cardiac total homocysteine (tHcy) reduced immediately in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (β: 0.115; 95% CI: 0.047∼0.183; p=0.001). tHcy reduction was more dramatic in left atrium than right (p<0.001), suggesting clearance through pulmonary circulation. Long-term effect of PFO closure was also monitored and compared to medical treatment alone (n=61). Complete PFO closure resulted in long-term tHcy reduction in peripheral blood, whereas medical therapy alone showed no effect (β: -0.208; 95% CI: -0.375∼-0.058; p=0.007). Residual shunting was again independently associated with persistently elevated tHcy (β: 0.184; 95% CI: 0.051∼0.316; p=0.007). CONCLUSIONS PFO shunting may contribute to circulatory tHcy elevation, which is renormalized by PFO closure. PFO is not just a door for clots, but may itself enhance clot formation and injure neurovasculature by clot-independent mechanisms. Biomarkers such as tHcy can potentially serve as cost-effective measures of residual shunting and neurovascular risk for PFO stroke.
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