Abstract W P398: PFO Closure Reduces High Homocysteine Level in Atrial Blood of Stroke Patients

Abstract

Background: PFO allows venous clots to bypass pulmonary filtration, leading to strokes. We previous found in metabolite screening that PFO endovascular closure lower markers of oxidative stress and homocysteine levels in peripheral venous blood. Here we study changes of homocysteine during endovascular closure in cardiac atrial blood to better understand the central metabolism of PFO in circulation. Method: PFO stroke patients are propectively recruited according to IRB approval with plasma sampled from left (LA) and right (RA) atria pre- and post- PFO closure (n=97). Total homocysteine (tHCY) level was measured by selected reaction monitoring using mass spectrometry. Result: tHCY level decreased significantly in both RA and LA post PFO closure (Fig. 1A, p = 0.0014; RA: reduced by 8.54% Fig. 1B, p = 0.0304; LA: reduced by 9.90% Fig. 1C, p = 0.0470). Notably, tHCY reduction was skewed towards patients with higher tHCY levels before PFO closure (Fig. 1D and E, Kolmogorov-Smirnov test, RA: p = 0.0413; LA: p = 0.0010), such that more patients with higher tHCY level had a more significant reduction in tHCY levels compared to those with lower/normal levels. Conclusion: We found that PFO closure efficiently reduced tHCY level in both venous and arterial systems of stroke patients with high tHCY level. This effect is more pronounced in patients with higher levels suggesting PFO closure may help change the pathophysiology of hyperhomocysteinemia; further studies are ongoing to understand the underlying mechanism.