Pulmonary Embolism and Right-to-Left Shunts

NCT07519876 | Recruiting

• 1 other identifier: STUDY00006524
• Study Type: observational
• Target: 256
• Locations: 1 country
• Sites: 1

Brief Summary

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:
• A second MRI of your brain will be performed.
• You will complete a questionnaire to evaluate whether you may have had a stroke since being discharged from the hospital
• You will meet with a member of the study team who will collect information about your health status.

Conditions

Pulmonary Arteriovenous Malformation; Pulmonary Embolism (PE); Right-to-Left Shunt; Stroke; Patent Foramen Ovale (PFO); Atrial Septal Defects

Keywords

Pulmonary Embolism; PE; Right-to-Left Shunt; PFO; ASD; Stroke; Atrial Septal Defects; Patent Foramen Ovale

Outcome Measures

Primary Outcomes (1)

• Combined incidence of acute ischemic stroke and silent cerebral infarct

  1. Acute ischemic stroke incidence through 90 days defined as an acute focal neurological deficit presumed to be due to focal cerebral or retinal ischemia and either: a) Persisting \>24 hours b) Persisting \<24 hours but associated with a neuroanatomically relevant cerebral or retinal infarct documented with MRI or CT or direct retinal observation. 2. Silent cerebral infarct through 90 days defined as the presence of at least one new hyperintense lesion of 3 mm or greater in diameter on T2-weighted MRI between the screening MRI and the 90-day MRI in the absence of a relevant clinical event.

  90 Days

Study Arms (2)

Right-to-Left Shunt (RLS)

The RLS cohort includes: a) Subjects found to have a right-to-left shunt (RLS) using transcranial Doppler (TCD) with bubble study b) Subjects with a known RLS (i.e. previously investigated with TCD or TEE)

No Right-to-Left Shunt (No RLS)

The No RLS cohort includes: a) Subjects with no RLS identified via TCD with bubble study b) Subjects known to not have an RLS (i.e. previously investigated with TCD or TEE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will be selected from the population of patients admitted to Tufts Medical Center

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Tufts Medical Center: lead
• Occlutech International AB: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Kasper W, Geibel A, Tiede N, Just H. Patent foramen ovale in patients with haemodynamically significant pulmonary embolism. Lancet. 1992 Sep 5;340(8819):561-4. doi: 10.1016/0140-6736(92)92102-l.

  PMID: 1355152 BACKGROUND

• Goliszek S, Wisniewska M, Kurnicka K, Lichodziejewska B, Ciurzynski M, Kostrubiec M, Golebiowski M, Babiuch M, Paczynska M, Koc M, Palczewski P, Wyzgal A, Pruszczyk P. Patent foramen ovale increases the risk of acute ischemic stroke in patients with acute pulmonary embolism leading to right ventricular dysfunction. Thromb Res. 2014 Nov;134(5):1052-6. doi: 10.1016/j.thromres.2014.09.013. Epub 2014 Sep 21.

  PMID: 25282541 BACKGROUND

• Doyen D, Castellani M, Moceri P, Chiche O, Lazdunski R, Bertora D, Cerboni P, Chaussade C, Ferrari E. Patent foramen ovale and stroke in intermediate-risk pulmonary embolism. Chest. 2014 Oct;146(4):967-973. doi: 10.1378/chest.14-0100.

  PMID: 24874409 BACKGROUND

• Clergeau MR, Hamon M, Morello R, Saloux E, Viader F, Hamon M. Silent cerebral infarcts in patients with pulmonary embolism and a patent foramen ovale: a prospective diffusion-weighted MRI study. Stroke. 2009 Dec;40(12):3758-62. doi: 10.1161/STROKEAHA.109.559898. Epub 2009 Sep 24.

  PMID: 19797184 BACKGROUND

• Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010 Apr;38(4 Suppl):S495-501. doi: 10.1016/j.amepre.2009.12.017.

  PMID: 20331949 BACKGROUND

MeSH Terms

Conditions

Pulmonary Embolism; Stroke; Heart Septal Defects, Atrial; Foramen Ovale, Patent; Pulmonary Arteriovenous Fistulas

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 9, 2026
• Study Start: January 30, 2026
• Primary Completion: February 18, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)