Plasma Proteomic Changes Persist In Long Term Follow-Up Of Patent Foramen Ovale Related Stroke Patients After Pfo Closure

Introduction: Paradoxical embolism from patent foramen ovale (PFO), a heterogeneous multi-organ condition involving brain, lung, heart and blood, lacks consensus for treatment options due to variability among individual patients. Clinical proteomic approaches may be promising for such complex diseases, where the disease process can be monitored in clinically accessible fluid such as blood. Here, we apply a pharmaco-proteomic approach to study PFO endovascular closure, an intervention that requires better risk stratification and monitoring of therapeutic efficacy to individualize treatment. Previously, we found that plasma small molecule signals such as serotonin, TSP-1 and microparticles -- which may avoid pulmonary filtration via PFO -- decrease immediately in the systemic circulation after effective PFO closure. Now we study the long-term effect of PFO endovascular closure. Methods/Results: To reduce confounders in an inherently complex system, the most robust clinical proteomic comparisons are those of profiles taken over time from the same individual. Accordingly, in consecutively recruited patients who underwent PFO closure (n=37), we analyze venous blood obtained prior to closure and in long-term followup (1-3 yrs) post closure. None of the subjects experienced recurrent TIA or strokes. More than 1 year post closure, plasma protein profiles -- in addition to the persistent decrease in small molecules such as serotonin -- continue to show a statistically significant (p<0.05) decrease of coagulation markers such as fibrinogen, fibrinogen fragments, D-dimer and others. Moreover, markers of inflammatory changes such as hsCRP, apolipoproteins and various immunoglobulins also remain decreased. Conclusion: A pharmaco-proteomic approach is clinically feasible and may help to monitor therapeutic efficacy, improve patient selection, and ensure more precise clinical phenotyping for clinical trials in PFO-related stroke. More than 1 year post PFO closure, relevant inflammatory and coagulation factors remain lowered after adjusting for other confounders such as medication changes. Further studies are needed to explore the utility of proteomic profiling to help individualize treatment in PFO-related strokes.