Emmanuelle Le Moigne, MD, PhD; Serge Timsit, MD, PhD; Douraied Ben Salem, MD, PhD; Romain Didier, MD, PhD; Yannick Jobic, MD, PhD; Nicolas Paleiron, MD, MS; Raphael Le Mao, MD, MS; Thierry Joseph, MD; Clément Hoffmann, MD; Angelina Dion, MS; Jean Rousset, MD, PhD; Grégoire Le Gal, MD, PhD; Karine Lacut, MD, PhD; Christophe Leroyer, MD, PhD; Dominique Mottier, MD; Francis Couturaud, MD, PhD
Presented in part at the 56th Annual Congress of the International Society on Thrombosis and Haemostasis, Berlin, Germany, 6–9 July 2017.
Note: All authors take responsibility for data access and integrity of the data.
Acknowledgment: The authors thank Ms. Zarrin Alavi, MSc, MEng (CIC INSERM 1412, Brest University Hospital), who critically reviewed the manuscript during its development and provided editorial assistance.
Grant Support: By grants from the Programme Hospitalier de Recherche Clinique (French Department of Health).
Disclosures: Dr. Timsit reports personal fees from Shire, Boehringer Ingelheim, FMC CHEM (DPC), FMC (SAMU), and HoliStick Medical and grants from AstraZeneca, Bayer, and Boehringer Ingelheim outside the submitted work. Dr. Le Gal reports that he is a co-investigator in clinical trials with Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, LEO Pharma, Daiichi Sankyo, and Bayer and has received honoraria from Bayer, Pfizer, LEO Pharma, Sanofi, and bioMérieux outside the submitted work. Dr. Leroyer reports grants, personal fees, and nonfinancial support from Bayer; nonfinancial support from Actelion, Daiichi Sankyo, LEO Pharma, and InterMune; personal fees and nonfinancial support from AstraZeneca; and grants and nonfinancial support from Pfizer outside the submitted work. Dr. Couturaud reports grants from Pfizer; personal fees from Bayer, Bristol-Myers Squibb, AstraZeneca, and LEO Pharma; and clinical trials with Bayer, Boeringher Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, AztraZeneca, GSK, and Actelion outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-3485.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: Available from Dr. Le Moigne (e-mail, email@example.com). Statistical code: Not available. Data set: Available from Dr. Le Moigne (e-mail, firstname.lastname@example.org) on reasonable request.
Corresponding Author: Emmanuelle Le Moigne, MD, Département de Médecine Interne et Pneumologie, Hôpital de la Cavale Blanche, CHRU de Brest, 29609 Brest cedex, France; e-mail, email@example.com.
Current Author Addresses: Drs. Le Moigne, Le Mao, Le Gal, Lacut, Leroyer, Mottier, and Couturaud: Brest University Hospital, Western Brittany University (UBO), Pneumology and Internal Medicine Unit, EA 3878, CIC INSERM 1412, Brest, France.
Dr. Timsit: Brest University Hospital, Western Brittany University (UBO), Neurology Unit, UMR 1078, Brest, France.
Dr. Ben Salem: Brest University Hospital, Western Brittany University (UBO), Radiology Unit, UMR 1101, Brest, France.
Drs. Didier and Jobic: Brest University Hospital, Western Brittany University (UBO), Cardiology Unit, EA 4324, Brest, France.
Dr. Paleiron: Toulon Military Hospital, Pneumology Unit, EA 3878, Toulon, France.
Dr. Joseph: Cornouaille Hospital Center, Cardiology Unit, Quimper, France.
Dr. Hoffman: Brest University Hospital, Western Brittany University (UBO), Vascular Medicine Unit, EA 3878, Brest, France.
Ms. Dion: Brest University Hospital, Western Brittany University (UBO), CIC INSERM 1412, Brest, France.
Dr. Rousset: Brest Military Hospital, Radiology Unit, Brest, France.
Author Contributions: Conception and design: E. Le Moigne, S. Timsit, Y. Jobic, G. Le Gal, C. Leroyer, D. Mottier, F. Couturaud.
Analysis and interpretation of the data: E. Le Moigne, S. Timsit, D. Ben Salem, R. Didier, Y. Jobic, A. Dion, G. Le Gal, K. Lacut, C. Leroyer, D. Mottier, F. Couturaud.
Drafting of the article: E. Le Moigne, S. Timsit, D. Ben Salem, Y. Jobic, C. Leroyer, D. Mottier, F. Couturaud.
Critical revision of the article for important intellectual content: E. Le Moigne, S. Timsit, R. Didier, Y. Jobic, C. Hoffmann, G. Le Gal, K. Lacut, C. Leroyer, D. Mottier, F. Couturaud.
Final approval of the article: E. Le Moigne, S. Timsit, D. Ben Salem, R. Didier, Y. Jobic, N. Paleiron, R. Le Mao, T. Joseph, C. Hoffmann, A. Dion, J. Rousset, G. Le Gal, K. Lacut, C. Leroyer, D. Mottier, F. Couturaud.
Provision of study materials or patients: E. Le Moigne, Y. Jobic, N. Paleiron, T. Joseph, K. Lacut, F. Couturaud.
Statistical expertise: E. Le Moigne, F. Couturaud.
Obtaining of funding: E. Le Moigne, S. Timsit, G. Le Gal, F. Couturaud.
Administrative, technical, or logistic support: R. Le Mao, K. Lacut, C. Leroyer, D. Mottier, F. Couturaud.
Collection and assembly of data: E. Le Moigne, S. Timsit, D. Ben Salem, R. Le Mao, J. Rousset, F. Couturaud.
Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism.
To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected.
Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423)
4 French hospital centers.
361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015.
Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment.
Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient.
Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]).
Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis.
Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO.
French Ministry of Health.
Le Moigne E, Timsit S, Ben Salem D, Didier R, Jobic Y, Paleiron N, et al. Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study. Ann Intern Med. [Epub ahead of print 7 May 2019]170:756–763. doi: 10.7326/M18-3485
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Published: Ann Intern Med. 2019;170(11):756-763.
Published at www.annals.org on 7 May 2019
Cardiology, Emergency Medicine, Neurology, Stroke, Venous Thromboembolism.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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