Pulmonary Embolism and Right-to-Left Shunts

Overview

Every fetus has a small hole in their heart, called a foramen ovale when they are developing in the womb. For most people this hole closes shortly after birth, but it doesn't close completely in 1 out of every 4 people. This is called a "patent" foramen ovale, or PFO. In people with a PFO it is possible for a blood clot in a vein to enter the heart, pass through the opening, and then go into an artery - this is referred to as a paradoxical embolism which passes through a "Right-to-Left Shunt," or RLS. If this occurs, the blood clot can cause a stroke. The most common RLS (more than 90%) is a PFO. Much rarer causes include other types of holes in the heart (like an atrial septal defect, or ASD), or a vascular communication in the lungs (like a pulmonary arteriovenous malformation, or AVM). We are investigating whether people with a PE are at higher risk of stroke if they happen to have an RLS compared to PE patients who don't have an RLS. This study will simply observe and compare the differences in stroke-related outcomes between those 2 groups. Participation in the study last roughly 90-days and includes the following activities: * The study team will review your medical records to collect general information such as your age, sex, race/ethnicity, height, weight, medications, medical history, and other medical information * Magnetic Resonance Imaging (MRI) of your brain will be done as soon as possible following your enrollment in the study. For more information on MRI scans, please see the "MRI scan" section below. * A Transcranial Doppler (TCD) with bubble study will be performed to determine if an opening is present in your heart or lungs. TCD is performed using ultrasound. A contrast called agitated saline will be injected into your vein for this test. * You will be asked to return for a follow-up visit 90 days after your pulmonary embolism. At this visit, the following will occur: 1. A second MRI of your brain will be performed. 2. You will complete a questionnaire to evaluate whether you may have had a stroke since being discharged from the hospital 3. You will meet with a member of the study team who will collect information about your health status.

Primary outcome measures

• Combined incidence of acute ischemic stroke and silent cerebral infarct [Time frame: 90 Days]

Eligibility criteria

Inclusion criteria

• Age ≥18
• Acute pulmonary embolism (any grade/size)
• Patient or legally authorized representative is able to provide consent to participate in the study

Exclusion criteria

• Patients who, in the opinion of the study investigators, are unable to participate in required study activities
• Patients unable to undergo MRI imaging

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Tufts Medical Center — Boston

Publications

• Zhang M, Tan S, Patel V, Zalta BA, Shmukler A, Levsky JM, Jain VR, Shaban NM, Haramati LB. Patent foramen ovale in patients with pulmonary embolism: A prognostic factor on CT pulmonary angiography? J Cardiovasc Comput Tomogr. 2018 Jul-Aug;12(4):271-274. doi: 10.1016/j.jcct.2017.11.009. Epub 2017 Dec 2. PMID 29217343
• Vindis D, Hutyra M, Sanak D, Kral M, Cechakova E, Littnerova S, Adam T, Precek J, Hudec S, Jecmenova M, Taborsky M. Patent Foramen Ovale and the Risk of Cerebral Infarcts in Acute Pulmonary Embolism-A Prospective Observational Study. J Stroke Cerebrovasc Dis. 2018 Feb;27(2):357-364. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.004. Epub 2017 Oct 12. PMID 29031497
• Tanislav C, Puille M, Pabst W, Reichenberger F, Grebe M, Nedelmann M, Kaps M, Allendorfer J. High frequency of silent pulmonary embolism in patients with cryptogenic stroke and patent foramen ovale. Stroke. 2011 Mar;42(3):822-4. doi: 10.1161/STROKEAHA.110.601575. Epub 2011 Jan 21. PMID 21257827
• Lucas TO, Schaustz EB, Dos Reis IJR, Lopes CG, Mendoca VS, Salluh JIF, Zukowski CN, Serafim RB. Risk of ischemic stroke in patients with pulmonary embolism and patent foramen ovale: A systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2025 Jan;34(1):108157. doi: 10.1016/j.jstrokecerebrovasdis.2024.108157. Epub 2024 Nov 30. PMID 39622459
• Lethen H, Flachskampf FA, Schneider R, Sliwka U, Kohn G, Noth J, Hanrath P. Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack. Am J Cardiol. 1997 Oct 15;80(8):1066-9. doi: 10.1016/s0002-9149(97)00604-8. PMID 9352979
• Le Moigne E, Timsit S, Ben Salem D, Didier R, Jobic Y, Paleiron N, Le Mao R, Joseph T, Hoffmann C, Dion A, Rousset J, Le Gal G, Lacut K, Leroyer C, Mottier D, Couturaud F. Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study. Ann Intern Med. 2019 Jun 4;170(11):756-763. doi: 10.7326/M18-3485. Epub 2019 May 7. PMID 31060047
• Lapergue B, Decroix JP, Evrard S, Wang A, Bendetowicz D, Offroy MA, Graveleau P, Russel S, Ramdane N, Mellot F, Scherrer A, Bourdain F. Diagnostic Yield of Venous Thrombosis and Pulmonary Embolism by Combined CT Venography and Pulmonary Angiography in Patients with Cryptogenic Stroke and Patent Foramen Ovale. Eur Neurol. 2015;74(1-2):69-72. doi: 10.1159/000437261. Epub 2015 Jul 25. PMID 26228469
• Konstantinides S, Geibel A, Kasper W, Olschewski M, Blumel L, Just H. Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism. Circulation. 1998 May 19;97(19):1946-51. doi: 10.1161/01.cir.97.19.1946. PMID 9609088

Identifiers

NCT: NCT07519876 · STUDY00006524

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗