Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb 6;319(5):452-462.
doi: 10.1001/jama.2017.21899.

Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke

Pauline Y Ng  1   2 , Andrew K-Y Ng  3   4 , Balachundhar Subramaniam  5 , Sara M Burns  1 , Fanny Herisson  6 , Fanny P Timm, Cand Med  1 , Maira I Rudolph, Cand Med  1 , Flora Scheffenbichler, Cand Med  1 , Sabine Friedrich, Cand Med  1 , Timothy T Houle  1 , Deepak L Bhatt  3 , Matthias Eikermann  1   5
Affiliations

Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke

Pauline Y Ng et al. JAMA. .

Abstract

Importance: Perioperative stroke is a major complication for patients undergoing surgery. Patent foramen ovale (PFO) represents a possible anatomical link between venous thrombosis and stroke.

Objective: To determine whether a preoperatively diagnosed PFO is associated with increased risk of perioperative ischemic stroke.

Design, setting, and participants: Retrospective cohort study from Massachusetts General Hospital and 2 affiliated community hospitals between January 1, 2007, and December 31, 2015. Participants were 182 393 consecutive adults undergoing noncardiac surgery with general anesthesia.

Exposures: Preoperatively diagnosed PFO.

Main outcomes and measures: Perioperative ischemic stroke occurring within 30 days of surgery; stroke subtype by Oxfordshire Community Stroke Project classification and stroke severity by National Institute of Health Stroke Scale (NIHSS).

Results: Among the 150 198 patient cases analyzed (median [SD] age, 55 [16] years), 1540 (1.0%) had a diagnosis of PFO before surgery. A total of 850 (0.6%) ischemic strokes occurred within 30 days of surgery (49 [3.2%] among patients with PFO and 801 [0.5%] among patients without PFO). In adjusted analyses, patients with PFO had an increased risk of ischemic stroke compared with patients without PFO (odds ratio, 2.66 [95% CI, 1.96-3.63]; P < .001). The estimated risks of stroke were 5.9 for every 1000 patients with PFO and 2.2 for every 1000 patients without PFO (adjusted absolute risk difference, 0.4% [95% CI, 0.2%-0.6%). Patients with PFO also had an increased risk of large vessel territory stroke (relative risk ratio, 3.14 [95% CI, 2.21-4.48]; P < .001) and a more severe stroke-related neurologic deficit measured by NIHSS (median, 4 [interquartile range {IQR}, 2-10] vs median, 3 [IQR, 1-6] for those without PFO; P = .02).

Conclusions and relevance: Among adult patients undergoing noncardiac surgery at 3 hospitals, having a preoperatively diagnosed PFO was significantly associated with increased risk of perioperative ischemic stroke within 30 days after surgery. Further research is needed to confirm these findings and to determine whether interventions would decrease this risk.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Subramaniam reports receipt of grants from NIGMS (PI [primary investigator]), Mallinckrodt Pharmaceuticals, DL Biotech, and Edwards Lifesciences. Dr Houle reports receipt of grants from NINDS (PI) and NIGMS; personal fees from the journals Headache: The Journal of Head and Face Pain, and Anesthesiology for statistical consulting, and personal fees from Cephalagia for expedited peer review outside the submitted work. Dr Bhatt reports receipt of personal fees for advisory board services from Elsevier Practice Update Cardiology, and other for advisory board services from Cardax, Medscape Cardiology, Regado Biosciences; other for board of directors participation from the Boston VA Research Institute and personal fees and nonfinancial support for board of directors participation (travel reimbursement) from the Society of Cardiovascular Patient Care; other for unfunded research collaboration from FlowCo, PLx Pharma, Takeda, and Merck; personal fees (honoraria) for participating on data monitoring committees from Duke Clinical Research Institute (and clinical trial steering committees), Mayo Clinic, Population Health Research Institute (also operations committee, publications committee, and steering committee for Bayer-funded trial [COMPASS]), Harvard Clinical Research Institute (St. Jude–funded trial [PORTICO]; and Boehringer Ingelheim–funded executive steering committee participation), Cleveland Clinic, and Mount Sinai School of Medicine; honoraria for editing from the American College of Cardiology (and travel reimbursement), Belvoir Publications, Slack Publications, HMP Communications (Journal of Invasive Cardiology), the Journal of the American College of Cardiology, and other from Clinical Cardiology; personal fees for CME steering committee participation from WebMD; other for site coinvestigator services from St. Jude Medical, Biotronik, and Boston Scientific; travel reimbursement from the American Heart Association as chair of the quality oversight committee; other for NCDR-Action Registry steering committee and VA CART research and publications committee participation; and royalties from Elsevier; all outside the submitted work. Dr Eikermann reports receipt of grants from Merck; personal fees (honoraria) from Merck; funding from Jeffrey and Judith Buzen; and holds equity in Calabash Bioscience. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Selection of Patients With vs Without Preoperatively Diagnosed Patent Foramen Ovale and Perioperative Ischemic Stroke Risk
aSome patients had more than 1 reason for exclusion. bPediatric surgeries include procedures performed by the pediatric surgical service, which are not limited to patients under 18 years. These procedures may be planned for congenital conditions, for example, fundoplication and repair of pectus excavatum. cThe American Society of Anesthesiologists (ASA) physical status classification system was used to evaluate patients’ physical state before undergoing anesthesia or surgery. Current definitions include 6 categories (ASA I [normal healthy patient] to ASA VI [patient with brain death]). dVasopressor dose is the total dose of inotropes and vasopressors used intraoperatively, including epinephrine, norepinephrine, phenylephrine, and dopamine, expressed in milligrams of norepinephrine equivalent.
Figure 2.
Figure 2.. Incidence of Stroke Among Low-Risk and High-Risk Stroke Patients, Stratified by Clinical Severity
The baseline patent foramen ovale (PFO)-independent risk of stroke was determined by a priori selected–variables (section 6.6 in Supplement 2). The study population was divided into low stroke risk and high stroke risk based on this baseline risk (sample size differs because 31 patients with American Society of Anesthesiologists [ASA] physical status class V were excluded due to failure to calculate the probability score [section 6.6 and eTable 5 in Supplement 2]). Stroke severity was stratified into minor stroke (National Institutes of Health Stroke Scale [NIHSS] scores 1-4), moderate stroke (NIHSS 5-14), and severe stroke (NIHSS 15-42). Patients with PFO had a higher incidence of stroke across all subgroups. For low-risk patients, the incidences of minor stroke (1 of 323 [0.31%] vs 24 of 74 761 [0.03%]; P = .006) and moderate stroke (1 of 323 [0.31%] vs 8 of 74 761 [0.01%]; P < .001) were higher among patients with PFO; there were no severe strokes. For high-risk patients, the incidences of minor stroke (16 of 1214 [1.32%] vs 331 of 73 869 [0.45%]; P < .001), moderate stroke (14 of 1214 [1.15%] vs 194 of 73 869 [0.26%]; P < .001), and severe stroke (6 of 1214 [0.49%] vs 49 of 73 869 [0.07%]; P < .001) were higher among patients with PFO.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Weiser TG, Haynes AB, Molina G, et al. . Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes. Lancet. 2015;385(suppl 2):S11. - PubMed
    1. Mashour GA, Shanks AM, Kheterpal S. Perioperative stroke and associated mortality after noncardiac, nonneurologic surgery. Anesthesiology. 2011;114(6):1289-1296. - PubMed
    1. Selim M. Perioperative stroke. N Engl J Med. 2007;356(7):706-713. - PubMed
    1. Mrkobrada M, Hill MD, Chan MT, et al. . Covert stroke after non-cardiac surgery: a prospective cohort study. Br J Anaesth. 2016;117(2):191-197. - PubMed
    1. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. 1984;59(1):17-20. - PubMed