This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers.
Methods Consecutive patients with PFO-related stroke 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 Patients with PFO-related stroke (n = 254) were recruited and followed up to 4 years (median 2.01; interquartile range 0.77–2.54). Metabolite profiling in the discovery cohort (n = 12) identified homocysteine as the most significantly decreased factor in intracardiac plasma after PFO closure (false discovery rate 0.001). This was confirmed in a validation cohort (n = 181), where intracardiac total homocysteine (tHcy) was immediately reduced in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (β 0.115; 95% confidence interval [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.
Glossary
- ANOVA=
- analysis of variance;
- AUC=
- area under the curve;
- CI=
- confidence interval;
- COPD=
- chronic obstructive pulmonary disease;
- FDR=
- false discovery rate;
- Hcy=
- homocysteine;
- HPLC=
- high-performance liquid chromatography;
- LA=
- left atrium/arterial;
- MCR2=
- Michigan Regional Comprehensive Metabolomics Resource Core;
- MGH=
- Massachusetts General Hospital;
- MS=
- mass spectrometry;
- OPLS-DA=
- orthogonal projections to latent structures-discriminant analysis;
- PFO=
- patent foramen ovale;
- qTOF=
- quadrupole time-of-flight;
- RA=
- right atrium;
- ROC=
- receiver operator characteristic;
- SOP=
- standard operating procedure;
- SRM=
- selected reaction monitoring;
- tHcy=
- total homocysteine;
- VIP=
- variable importance for projection
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 55
- Received July 6, 2020.
- Accepted in final form April 13, 2021.
- © 2021 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
- Reader Response: Effect of Patent Foramen Ovale Closure After Stroke on Circulatory Biomarkers
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Topics Discussed
Alert Me
Recommended articles
Practice advisory update summary: Patent foramen ovale and secondary stroke prevention
Recurrent cerebral ischemia in medically treated patent foramen ovale
An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke
Percutaneous patent foramen ovale closure for secondary stroke prevention