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

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012188
Author(s):  
Wenjun Deng ◽  
David McMullin ◽  
Ignacio Inglessis-Azuaje ◽  
Joseph J. Locascio ◽  
Igor F. Palacios ◽  
...  
Keyword(s):  
Patent Foramen Ovale ◽  
Venous Blood ◽  
Cost Effective ◽  
Foramen Ovale ◽  
Stroke Patients ◽  
Discovery Cohort ◽  
Long Term Effect ◽  
Serial Sampling ◽  
Pfo Closure

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.

Abstract TP430: Plasma Proteomic Changes Persist in Long Term Follow-up of Patent Foramen Ovale Related Stroke Patients after PFO Closure

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
MingMing Ning ◽  
Mary Lopez ◽  
David A Sarracino ◽  
Kathleen Feeney ◽  
Molly Thayer ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Patent Foramen Ovale ◽  
Venous Blood ◽  
Disease Process ◽  
Foramen Ovale ◽  
Proteomic Profiling ◽  
Proteomic Approach ◽  
Individualize Treatment ◽  
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.

scholarly journals 15: PFO CLOSURE REDUCES PLASMA LEVELS OF SEROTONIN IN A LONG TERM FOLLOWUP OF STROKE PATIENTS

2016 ◽  
Vol 64 (3) ◽  
pp. 812.3-813
Author(s):  
W Deng ◽  
D McMullin ◽  
T Wickham ◽  
K Feeney ◽  
I Inglessis ◽  
...  
Keyword(s):  
Venous Blood ◽  
Stroke Patients ◽  
Peripheral Venous Blood ◽  
Vasoactive Factors ◽  
Long Term Effect ◽  
Anxiety Depression ◽  
Medication Status ◽  
Pfo Closure

Purpose of StudyPFO allows venous clots and vasoactive factors to bypass pulmonary filtration and remain in circulation. We previously identified an immediate reduction of procoagulant serotonin (5-HT) in left atrial blood post PFO closure. To understand the long-term effect of PFO closure, we report the change of 5-HT in peripheral venous blood in 1-year followup.Methods Used97 PFO-related stroke patients were recruited on IRB approval. Venous blood was collected at baseline (BL) and 1 year follow-up (FU) of treatments (PFO closure and medical therapy). Plasma 5-HT was quantified by mass spectrometry. Patients with serotonin modifying medications (ie. SSRIs) or conditions (anxiety/depression) were excluded.Summary of Results5-HT level in peripheral venous blood was significantly reduced by 27.27% (BL: 7.57±8.04 µM; FU: 5.51±5.72 µM; p=0.0034) in 61 patients receiving PFO closure (figure 1A). In the 37 PFO patients treated with medicine alone, no changes were observed (BL: 5.79±7.15 µM; FU: 6.25±6.68 µM; p=0.4050) (figure 1B). 5-HT reduction was independently associated with PFO closure after adjusting for age, gender, medical history and medication status in a multivariate regression (figure 1C).ConclusionsWe found that PFO closure independently reduced 5-HT level in peripheral venous blood. These results support the hypothesis that PFO related right-to-left interatrial shunt may foster higher level of procoagulant and vascoactive substances in circulation. While PFO closure decrease prothrombotic markers immediately post closure, this effect is sustained in long term followup up to 1 year. Further studies on the clinical outcome of these PFO patients with respect to their prothrombotic circulatory profiles are ongoing.Abstract 15 Figure 1

scholarly journals Efficacy of patent foramen ovale closure for treating migraine: a prospective follow-up study

2020 ◽  
Vol 69 (1) ◽  
pp. 7-12
Author(s):  
Yi Qi ◽  
Yushun Zhang ◽  
Xiaohui Luo ◽  
Gesheng Cheng ◽  
Yajuan Du ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Patent Foramen Ovale ◽  
Foramen Ovale ◽  
Residual Shunt ◽  
Vas Score ◽  
Long Term Effect ◽  
The Difference ◽  
Pfo Closure

This study aims to evaluate the potential of percutaneous patent foramen ovale (PFO) closure to improve the headache in patients with migraine and PFO, and discuss the difference between the randomized controlled trials (RCTs) and the single-center studies. Patients of migraine with a large shunt of PFO, who experienced ≥2 headache attacks per month and failed ≥2 categories of standardized medication, underwent PFO closure in First Affiliated Hospital of Xi'an Jiao Tong University. The clinical outcomes, including frequency and duration of headache attacks, Headache Impact Test (HIT-6) score, and Visual Analogue Scale (VAS) score, were evaluated at 3, 6, and 12 months of follow-up after the PFO closure. The different efficacies of the clinical outcomes between patients with and without aura as well as different grades of PFO were also evaluated, respectively. 134 patients with migraine (39 male and 95 female) with PFO were enrolled, whose average age was 39.21±11.37 years. After PFO closure, there was a significant reduction in frequency and duration of headache attacks, HIT-6 score, and VAS score at 3, 6, and 12 months’ follow-up (p<0.001). Migraine was completely relieved in 54 (40.30%) patients during 12 months’ follow-up. The frequency of migraine was reduced by >50% in 44 (32.84%) patients at 3 months’ follow-up and increased to 48 (35.82%) at 12 months’ follow-up. 31.03% patients remained residual shunt after 6 months of closure with varying improvements of headache. This study confirmed that PFO closure can effectively reduce frequency and duration of migraine and improve quality of life, but the definitive indications and long-term effect still need further research.

Abstract TP426: PFO Closure Reduces Plasma Levels of Serotonin in Long Term Follow up of Stroke Patients

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Wenjun Deng ◽  
David McMullin ◽  
Thomas Wickham ◽  
Kathleen Feeney ◽  
Ignacio Inglessis ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Venous Blood ◽  
Stroke Patients ◽  
Peripheral Venous Blood ◽  
Vasoactive Substances ◽  
Long Term Effect ◽  
Long Term Follow Up ◽  
Pfo Closure

Background: PFO allows venous clots and vasoactive circulatory factors to bypass pulmonary filtration and remain in circulation. Serotonin (5-HT) has procoagulant and oxidative roles in both cardiovascular and neurovascular injury. We previously identified an immediate reduction of 5-HT in left atrial blood post PFO closure. To understand the long-term effect of PFO closure, we report the changes of 5-HT in peripheral venous blood in 1-year follow-up. Method: 97 PFO-related stroke patients were recruited in accordance with IRB. Venous blood was collected at baseline (BL) and 1 year follow-up (FU) post treatment (PFO closure or medical therapy). Plasma 5-HT was quantified by mass spectrometry. Patients with serotonin modifying medications (e.g. SSRIs) or conditions (e.g. anxiety/depression) were excluded. Result: 5-HT concentration in peripheral venous blood was significantly reduced by 27.27% (BL: 7.57 ± 8.04 μmol/l; FU: 5.51 ± 5.72 μmol/l; p = 0.0034) in 61 patients receiving PFO closure (Fig 1A). In the 37 PFO patients treated with medical therapy alone, no changes were observed (5-HT: BL: 5.79 ± 7.15 μmol/l; FU: 6.25 ± 6.68 μmol/l; p = 0.4050) (Fig 1B). This decrease in serotonin was independently associated with PFO closure after adjusting for age, gender, medical history and medication status in a multivariate regression (Fig 1C). Conclusion: We found that PFO closure independently reduced 5-HT level in peripheral venous blood. These results support the hypothesis that PFO associated right-to-left interatrial shunting may foster higher levels of procoagulant and vasoactive substances in circulation. We have previously found PFO closure to decrease prothrombotic markers immediately post closure; this effect is now shown also to be sustained in long term follow-up up to 1 year. Further studies are ongoing on the clinical outcome of these PFO related stroke patients with respect to their prothrombotic circulatory profiles.

Abstract T P114: Effect Endovascular Closure Procedure on the Quality of Life in Stroke Patients with Patent Foramen Ovale

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Kathleen Feeney-Heinzelmann ◽  
Wenjun Deng ◽  
Thomas Wickham ◽  
Mikaela Elia ◽  
Ignacio Inglessis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Patent Foramen Ovale ◽  
Stroke Severity ◽  
Depression And Anxiety ◽  
Foramen Ovale ◽  
Stroke Patients ◽  
Stroke Risk Factor ◽  
Pfo Closure

Introduction: Patent foramen ovale (PFO), an opening between the left and right atria, is an independent stroke risk factor associated with more than 150,000 strokes per year in the US. PFO stroke patients tend to be younger - most are of child bearing age, enjoy an active lifestyle and are a major component of the work force, who are not long-term anticoagulant candidates. While trials are ongoing to compare closure vs medical treatment, younger stroke patients tend to prefer endovascular closure rather than long-term anticoagulation. Here we investigate the effect of PFO closure for stroke prevention on patients’ quality of life. Methods: Patients were recruited per IRB-approved protocol from the MGH Cardio-Neurology Clinic. To quantify the effect of PFO closure on depression and anxiety, validated Becks Depression and Anxiety Inventory were performed by research nurses at 3 months before and 3-6 months after PFO closure. Clinical data on stroke severity, outcome and blood samples were also collected. Results: 32 consecutive PFO stroke patients, adjudicated by two vascular neurologists (average age 50.75, range 22-59; 56% male) were enrolled. No new treatments (e.g. anti-depressant/anti-anxiety meds) were initiated during the study. After successful PFO closure, patients had significantly improved anxiety (3 vs 5.75, p= 0.043) and depression scores (2.58 vs 3, p= 0.05) (Figure). Cortisol level also lowered post PFO closure (data not shown due to space). Conclusion: PFO stroke patients have improved quality of life after PFO closure as measured by validated quantitative anxiety and depression scales under the care of a team of nurses, physicians and neuropsychologist. These findings demonstrate the importance of a multi-disciplinary approach to stroke patient care, and also the effect of endovascular closure in improving the quality of life in younger stroke patients. Future studies are needed in a larger cohort with long term follow-up to validate these results.

scholarly journals Short- and long-term haemodynamic consequences of transcatheter closure of atrial septal defect and patent foramen ovale

2021 ◽  
Author(s):  
X. Jin ◽  
Y. M. Hummel ◽  
W. T. Tay ◽  
J. F. Nauta ◽  
N. S. S. Bamadhaj ◽  
...  
Keyword(s):  
Atrial Septal Defect ◽  
Diastolic Function ◽  
Patent Foramen Ovale ◽  
Septal Defect ◽  
Transcatheter Closure ◽  
Foramen Ovale ◽  
Short And Long Term ◽  
Interatrial Shunt ◽  
Pfo Closure

Abstract Background Transcatheter atrial septal defect (ASD) and patent foramen ovale (PFO) closure might have opposite short- and long-term haemodynamic consequences compared with restricted interatrial shunt creation, which recently emerged as a potential treatment modality for patients with heart failure with preserved ejection fraction (HFpEF). Given the opposing approaches of ASD and PFO closure versus shunt creation, we investigated the early and sustained cardiac structural and functional changes following transcatheter ASD or PFO closure. Methods In this retrospective study, adult secundum-type ASD and PFO patients with complete echocardiography examinations at baseline and at 1‑day and 1‑year follow-up who also underwent transcatheter closure between 2013 and 2017 at the University Medical Centre Groningen, the Netherlands were included. Results Thirty-nine patients (mean age 48 ± standard deviation 16 years, 61.5% women) were included. Transcatheter ASD/PFO closure resulted in an early and persistent decrease in right ventricular systolic and diastolic function. Additionally, transcatheter ASD/PFO closure resulted in an early and sustained favourable response of left ventricular (LV) systolic function, but also in deterioration of LV diastolic function with an increase in LV filling pressure (LVFP), as assessed by echocardiography. Age (β = 0.31, p = 0.009) and atrial fibrillation (AF; β = 0.24, p = 0.03) were associated with a sustained increase in LVFP after transcatheter ASD/PFO closure estimated by mean E/e’ ratio (i.e. ratio of mitral peak velocity of early filling to diastolic mitral annular velocity). In subgroup analysis, this was similar for ASD and PFO closure. Conclusion Older patients and patients with AF were predisposed to sustained increases in left-sided filling pressures resembling HFpEF following ASD or PFO closure. Consequently, these findings support the current concept that creating a restricted interatrial shunt might be beneficial, particularly in elderly HFpEF patients with AF.

D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale

2015 ◽  
Vol 114 (09) ◽  
pp. 614-622 ◽  
Author(s):  
Young Dae Kim ◽  
Dongbeom Song ◽  
Hyo Suk Nam ◽  
Kijeong Lee ◽  
Joonsang Yoo ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Patent Foramen Ovale ◽  
Pulmonary Thromboembolism ◽  
Cryptogenic Stroke ◽  
Foramen Ovale ◽  
Stroke Patients ◽  
Term Outcome ◽  
Long Term Outcome ◽  
D Dimer

SummaryPatent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648–17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

scholarly journals Long-Term Outcome Following Patent Foramen Ovale (PFO) Closure

2017 ◽  
Vol 26 ◽  
pp. S215-S216
Author(s):  
K. Balakrishnan ◽  
G. Koshy ◽  
B. Thompson ◽  
B. Herman
Keyword(s):  
Patent Foramen Ovale ◽  
Foramen Ovale ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Pfo Closure

scholarly journals Role of transoesophageal echocardiography in detecting patent foramen ovale in stroke patients aged ≤60 years: A retrospective study

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242885
Author(s):  
Reabal Najjar ◽  
Andrew Hughes
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Patent Foramen Ovale ◽  
Stroke Unit ◽  
Transoesophageal Echocardiography ◽  
Inverse Association ◽  
Foramen Ovale ◽  
Stroke Patients ◽  
Venous Thromboembolic Events ◽  
Pfo Closure

Background The underlying aetiology of ischaemic strokes is unknown in as many as 50% of cases. Patent foramen ovale (PFO) has become an increasingly recognised cause of ischaemic strokes in young patients. The present study aimed (1) to assess the frequency of transoesophageal echocardiography (TOE) performed and the proportion of PFOs detected in patients aged ≤60 years and (2) examine the effect of PFO closure on reducing stroke reoccurrence. Methods This was a retrospective clinical audit based on de-identified, secure medical records of the Canberra Hospital, Australia. A review of records was conducted on discharged patients aged 18–60 years admitted to the stroke unit following an ischaemic stroke episode between January 1, 2015, and December 31, 2018. Results A total of 214 acute ischaemic stroke patients were admitted to the stroke unit (mean age, 49.2 ± 9.7 years). Concerning aetiology, 47.2% were cryptogenic in origin, whereas 52.8% had a stroke of a determined cause. 12 patients were diagnosed with a PFO and 7 venous thromboembolic events were identified, 1 in the cryptogenic group and 6 in the determined cause group. 91.7% of PFOs were diagnosed in patients with a cryptogenic stroke. Trans-thoracic echocardiography (TTE) was performed in 37.3% of patients and had detected 4 PFOs (sensitivity 27.3%, specificity 92.5%). TOE was performed in 26.2% of patients and had detected 11 PFOs (sensitivity 90.0%, specificity 100%). The number needed to treat to prevent the occurrence of an ischaemic stroke through PFO closure was estimated at 30. Conclusions An inverse association between age and PFO presence was found in patients aged 18–60 years. Additionally, TOE was superior to TTE for detecting PFO, particularly in those with stroke of an undetermined cause. Our results suggest an increased need for TOE as a routine imaging procedure for acute ischaemic stroke patients aged ≤60.

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