Metabolomic analysis of PFO-related stroke shows immediate and persistent decrease of homocysteine post PFO closure (P2.277)

Objective We aimed to find out the small molecules affected by PFO closure. The changes of these factors should be closely related to the pathology of PFO-related stroke. Background PFO can increase the risk of stroke by enabling direct mixing of venous and arterial circulation and serving as a conduit for venous clots. Our previous study found that PFO disturbs pulmonary filtration of harmful factor, serotonin (5HT), which stays high in circulation and creates a prothrombotic state. In the context of endovascular PFO closure, a bedside model to understand PFO circulatory signaling, we performed a full metabolomic profile of other mediators that may respond to PFO closure. Method Patients were recruited in accordance with IRB approval. Plasma was sampled from left (LA) and right (RA) atria pre and post PFO closure and also from venous 3 months post closure. A discovery metabolite screening was performed in 14 patients and analysis was performed with one-way ANOVA. Result With strict analysis (537 metabolites, one-way ANOVA, p<0.01), we identified homocysteine (HCY) with the most prominent change after PFO closure. While HCY levels in the left atrium (LA) and right atrium (RA) were comparable pre-closure (pre-LA: 5.61±0.09; pre-RA: 5.30±0.48), HCY immediately decreased in LA post closure (post-LA: 4.56±0.04) and remained low in peripheral venous blood at 3-month follow-up (4.57±0.06; p=0.0036). Conclusion We found PFO closure to lower HYC immediately in left atrial (arterial) blood, and this effect persists in peripheral venous circulation at 3 months post procedure. Since high level of HYC is independently associated with stroke and heart disease, our results suggest that mechanical PFO repair may improve circulatory profile of PFO stroke patients. Studies in a larger patient cohort and validation of other important metabolites are ongoing. Disclosure: Dr. Deng has nothing to disclose. Dr. Beecher has nothing to disclose. Dr. Burant has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. De Jong has nothing to disclose. Dr. Palacios has nothing to disclose. Dr. Inglessis has nothing to disclose. Dr. Silverman has nothing to disclose. Dr. Feeney has nothing to disclose. Dr. Elia has nothing to disclose. Dr. Wickham has nothing to disclose. Dr. McMullin has nothing to disclose. Dr. Dec has nothing to disclose. Dr. Buonanno has nothing to disclose. Dr. Eng H has nothing to disclose. Dr. Ning has nothing to disclose.