Abstract
Background: PFO, an independent stroke risk factor, enables direct mixing of venous and arterial circulation. As we have found previously, PFO serves not only as a conduit for venous clots, but also enables harmful factors such as serotonin (5HT) to avoid pulmonary filtration to remain within circulation at elevated levels, potentially contributing to a prothrombotic state. We hypothesize that in addition to 5HT, other factors may also be involved. In the context of endovascular PFO closure, a bedside model to understand PFO circulatory signaling, we performed a full metabolomic profile of mediators that may respond to PFO closure. Method: Non-migraine stroke patients were recruited in accordance with IRB approval, plasma was sampled from left and right atria pre and post closure and also from venous blood 3 months post PFO closure. A discovery metabolite screening was performed in 14 patients who underwent PFO closure, and analysis was performed using one-way ANOVA. Result: After stringent data filtering (537 metabolites, one-way ANOVA, p-value <0.01), we identified significant changes in a panel of small molecules after PFO closure - the most prominent change being in homocysteine (HCY). While relative HCY levels (expressed as peak area) 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 PFO closure (post-LA: 4.56 ± 0.04) and HCY level 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.
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