Assessing Stroke Risk During Surgery for Patent Foramen Ovale

(CAPPRES Trial)

Overseen By Eric Horlick, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Anticoagulants

Disqualifiers: Stroke risk, MRI contraindications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 33

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a condition called patent foramen ovale (PFO), a small hole in the heart, increases the risk of stroke during non-cardiac, non-vascular, and non-neurological surgery. The researchers will use imaging tests such as Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) and Transcranial Doppler (TCD) ultrasound to detect signs of stroke before and after surgery. The study seeks patients undergoing surgeries on areas like the spine or general regions who will remain in the hospital for at least two days. As an unphased trial, this study provides patients the opportunity to contribute to important research that could enhance surgical safety for many.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you need long-term anticoagulants, you cannot participate in the trial.

What prior data suggests that these imaging techniques are safe for assessing stroke risk?

Research shows that the treatments in this study—Diffusion-weighted Magnetic Resonance Imaging (DW-MRI), Transcranial Doppler (TCD), and Transthoracic Echocardiogram (TTE)—are generally safe.

Studies indicate that DW-MRI is commonly used to find brain lesions without causing harm. In one study, 58% of participants had detectable lesions, but these tests are non-invasive and well-tolerated.

TCD, another non-invasive imaging tool, accurately identifies high-risk cases of patent foramen ovale (PFO). No significant safety issues have been reported with its use.

TTE, similar to an ultrasound of the heart, is safe and does not involve radiation. It is a common test and generally causes no side effects.

These tests are routine in medical settings and have not been linked to adverse events in the reviewed research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Diffusion-weighted Magnetic Resonance Imaging (DW-MRI), Transcranial Doppler (TCD), and Transthoracic Echocardiogram (TTE) to assess stroke risk during surgery for individuals with a patent foramen ovale (PFO) because these non-invasive imaging techniques offer unique insights. DW-MRI provides detailed images of brain tissue, helping to detect silent strokes that might occur during surgery. TCD measures blood flow velocity in the brain's major arteries, potentially identifying microemboli that could lead to strokes. TTE, on the other hand, offers a clear view of the heart, allowing for the detection of PFOs that could be responsible for emboli. Together, these methods could significantly enhance our understanding of stroke risk during surgery, offering a more comprehensive approach than traditional methods like clinical observation and standard imaging techniques.

What evidence suggests that this trial's treatments could be effective for assessing stroke risk during surgery for PFO?

In this trial, participants will undergo assessments using Diffusion-weighted Magnetic Resonance Imaging (DW-MRI), Transcranial Doppler (TCD), and Transthoracic Echocardiogram (TTE) to evaluate stroke risks during surgery for Patent Foramen Ovale (PFO). Previous studies have shown that DW-MRI effectively detects ischemic lesions, with a detection rate over 95%, making it excellent at identifying stroke-related changes in the brain. TCD is 95% effective at finding a PFO, a hole in the heart that didn't close properly after birth and is a common cause of stroke. TTE also helps guide treatments for PFO, making procedures faster and potentially safer. Each of these tools plays a crucial role in identifying and understanding stroke risks linked to PFO. ^{3 6 7 8 9}

Who Is on the Research Team?

Lusine Abrahamyan, MD, PhD

Principal Investigator

University Health Network, Theta Collaborative

Eric Horlick, MD

Principal Investigator

University Health Network, Peter Munk Cardiac Centre

Aleksandra Pikula, MD

Principal Investigator

University Heath Network, Division of Neurology

Are You a Good Fit for This Trial?

This study is for adults over 18 who are scheduled for elective non-cardiac, non-vascular, and non-brain surgeries with a hospital stay of at least 2 days. It includes general, orthopedic, urological, gynecologic, spinal or thoracic surgeries. People on long-term blood thinners or those with conditions that raise stroke risk can't join.

Inclusion Criteria

I am referred for surgery in general, orthopedic, urology, gynecology, spine or chest areas.

I am expected to stay in the hospital for 2 days or more.

I am scheduled for surgery that is not related to my heart, blood vessels, or brain.

Exclusion Criteria

I cannot follow the study's requirements.

I need long-term blood thinners around the time of surgery.

I have health conditions that could raise my risk of stroke during surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Pre-operative

1 visit (in-person) during surgery pre-admission clinic

Pre-operative Assessment

Patients undergo PFO screening using transcranial Doppler (TCD) and transthoracic echocardiography (TTE)

Pre-operative

1 visit (in-person)

Postoperative Monitoring

DW-MRI conducted between postoperative days 2 and 7 to identify perioperative stroke incidence

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including phone surveys and cognitive assessments

1 year

Phone surveys at 30-day and 1-year post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• Diffusion-weighted Magnetic Resonance Imaging (DW-MRI)
• Transcranial Doppler (TCD)
• Transthoracic Echocardiogram (TTE)

Trial Overview The trial is investigating if having an asymptomatic PFO increases the risk of strokes around the time of surgery. Participants will undergo special imaging tests like DW-MRI and TCD to monitor their brain health before and after surgery.

How Is the Trial Designed?

Group I: Surgical patients Experimental Treatment 3 Interventions

Patients undergoing major non-cardiac, non-vascular, and non-brain surgery who will be examined for a presence of PFO

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Peter Munk Cardiac Centre

Collaborator

Trials

2

Recruited

910+

Published Research Related to This Trial

Diffusion-weighted magnetic resonance imaging (DWI) is highly effective in detecting ischemic lesions in stroke patients, with a detection rate exceeding 95%, but false negatives can occur, especially with small lesions in the brainstem, necessitating further diagnostic evaluation.

In transient ischemic attack (TIA) patients, DWI lesions are found in 1 in 6 to 2 in 3 cases, and the characteristics of these lesions can provide insights into stroke etiology and help tailor treatment for secondary prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical significance of diffusion-weighted MR imaging in stroke and TIA patients. Engelter, ST., Wetzel, SG., Bonati, LH., et al.[2022]

In a study of 75 patients undergoing patent foramen ovale (PFO) closure, cardiac magnetic resonance imaging (CMRI) was found to be less effective than transesophageal echocardiography (TEE) in detecting atrial septal aneurysms (ASA) and right-to-left shunting, with CMRI identifying ASA in 37.3% of cases compared to 62.7% with TEE.

Despite its limitations, CMRI was able to detect moderate to severe shunts in 66.6% of cases, indicating that while it may not be the best for certain assessments, it still provides valuable information in the evaluation of cardiac conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac magnetic resonance imaging and transesophageal echocardiography in patients with transcatheter closure of patent foramen ovale. Nusser, T., Höher, M., Merkle, N., et al.[2016]

Transthoracic echocardiography (TTE) often fails to detect partial patent foramen ovale (PFO), which can lead to missed diagnoses of PFO-associated strokes, as demonstrated in a case of a 60-year-old male with recurrent stroke symptoms despite normal TTE results.

Contrast-enhanced transcranial Doppler proved effective in identifying right-to-left shunts, suggesting it should be used as a supplementary tool for stroke investigations and PFO screening to improve diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patent foramen ovale-associated stroke repeatedly misdiagnosed as cerebral small vessel disease: A case report. Zhang, Y., Zhu, R., Yu, Z., et al.[2023]

The study demonstrates the effectiveness of using a combination of contrast transthoracic echocardiography and transcranial Doppler ultrasound to identify and select emboli for treatment in a patient with a patent foramen ovale.

This approach may enhance the safety and precision of interventions aimed at preventing stroke in patients with this heart condition by accurately targeting emboli in the cerebral circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Doppler detection of middle cerebral artery emboli before and after surgical closure of a patent foramen ovale. Doherty, EA.[2019]

A strong association was found between patent foramen ovale (PFO) and cryptogenic ischemic stroke in a study of 124 patients under 51 years old, with an odds ratio of 4.3, indicating that PFO may be a significant risk factor for this type of stroke.

Transcranial Doppler (TCD) was shown to be an excellent diagnostic tool for detecting PFO, with sensitivity and specificity values above 85%, suggesting it can effectively identify patients who may benefit from further investigation and potential closure of the PFO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abnormalities of interatrial septum and ischemic stroke in young people]. Negrão, EM., Brandi, IV., Nunes, SV., et al.[2019]

In a study of 55 patients with acute anterior circulation stroke or TIA, diffusion-weighted MRI (DWI) was found to be more effective than transcranial Doppler ultrasonography (TCD) in detecting ischemic lesions, revealing lesions in 33 out of 44 patients without microembolic signals (MES).

While TCD detected microembolic signals in some cases, DWI provided clearer insights into stroke etiology, suggesting that DWI should be prioritized in acute stroke assessments, although longer TCD monitoring might improve its diagnostic value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffusion weighted MRI imaging and MES detection in the assessment of stroke origin. Droste, DW., Knapp, J., Freund, M., et al.[2007]

In a study of 27 patients undergoing pulmonary vein isolation for atrial fibrillation, 22% developed silent cerebral ischemia (SCI) post-ablation, as revealed by diffusion-weighted MRI.

The study found that a higher count of micro-embolic signals (MESs) detected during the procedure was significantly associated with new SCI, particularly in patients older than 68 years, indicating that monitoring MESs could help predict the risk of SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral micro-embolization during pulmonary vein isolation: Relation to post-ablation silent cerebral ischemia. Nagy-Baló, E., Martirosyan, M., Sándorfi, G., et al.[2018]

In a study of 32 patients with newly diagnosed atrial fibrillation and left atrial thrombi, 34% showed signs of cerebral embolism at the start, indicating a high prevalence of clinically silent emboli that has been previously underestimated.

Despite continuous anticoagulation therapy, 13% of patients developed new cerebral emboli over 12 months, and only 63% of atrial thrombi resolved completely, highlighting the need for careful monitoring and management in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term fate of left atrial thrombi and incidence of cerebral embolism under continuous anticoagulation therapy]. Strach, K., Meyer, C., Hackenbroch, M., et al.[2019]

In a study of 39 patients undergoing aneurysmal coil embolization, 43.6% showed hyperintense lesions on diffusion-weighted imaging (DWI), indicating a significant occurrence of thromboembolic events, with 17.9% experiencing acute thromboembolic infarction and 35.9% having silent microembolisms.

The study found that using a left side approach during the procedure significantly increased the risk of silent microembolisms, suggesting that careful handling of guiding catheters is crucial to minimize this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Silent microembolism on diffusion-weighted MRI after coil embolization of cerebral aneurysms. Sim, SY., Shin, YS.[2021]

Transcranial Doppler sonography (TCD) using galactose microbubbles is a reliable method for screening patent foramen ovale (PFO), with a high sensitivity of 93% and specificity of 100% when compared to transesophageal echocardiography in a study of 50 patients.

The use of the Valsalva maneuver during TCD is crucial for accurate detection, as it helps prevent false-negative results, ensuring that the test effectively identifies patients at risk for stroke due to PFO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of transesophageal echocardiography and transcranial Doppler sonography with contrast medium for detection of patent foramen ovale. Jauss, M., Kaps, M., Keberle, M., et al.[2019]

In a study of 38 cerebrovascular patients, transcranial Doppler sonography (TCD) effectively detected a patent foramen ovale (PFO), with 30 patients showing positive results, particularly when contrast was injected before the Valsalva maneuver (VM).

The timing of contrast injection significantly influenced the detection of microbubbles, with the highest number observed when injected before VM, indicating this method is optimal for assessing right-to-left shunts through a PFO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patent foramen ovale and transcranial Doppler. Comparison of different procedures. Zanette, EM., Mancini, G., De Castro, S., et al.[2022]

In a study of 22 patients with acute ischemic stroke, transcranial Doppler (TCD) ultrasound showed potential markers for identifying salvageable brain tissue, indicated by a perfusion-diffusion mismatch, which is typically assessed using MRI.

The combination of specific TCD parameters (MCA CBFV asymmetry of ≥30% and ICA-to-MCA gradient of ≥20 cm/sec) demonstrated a sensitivity of 75% and specificity of 80% for detecting mismatch, suggesting TCD could be a practical alternative to MRI in acute stroke evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Doppler markers of diffusion-perfusion mismatch. Restrepo, L., Razumovsky, AY., Ziai, W., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05592301

Patent Foramen Ovale (PFO) and Risk of Perioperative ... The Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) is used to diagnose perioperative stroke. Diagnostic Test : Transcranial Doppler (TCD). Used to ...

2. withpower.com withpower.com/trial/phase-patent-foramen-ovale-pfo-9-2022-8fb1b

Assessing Stroke Risk During Surgery for Patent Foramen ... Diffusion-weighted magnetic resonance imaging (DWI) is highly effective in detecting ischemic lesions in stroke patients, with a detection rate exceeding 95 ...

3. journals.lww.com journals.lww.com/md-journal/fulltext/2025/05230/a_patient_with_patent_foramen_ovale_associated.67.aspx

A patient with patent foramen ovale associated ischemic... Magnetic resonance imaging (MRI) of patients with patent foramen ovale (PFO)-associated stroke often shows scattered, multiple ischemic ...

4. ahajournals.org ahajournals.org/doi/abs/10.1161/STROKEAHA.121.034451

Patent Foramen Ovale Closure Decreases the Incidence ... The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12114012/

A patient with patent foramen ovale associated ischemic ... In this report, we discuss a patient with PFO-associated ischemic stroke combined with hemorrhagic transformation (HT) to provide a basis for the diagnosis and ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMc1714320

Trials of Patent Foramen Ovale Closure The risk of stroke was lower with patent foramen ovale (PFO) closure than with medical therapy alone.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4635723/

Patent Foramen Ovale and Stroke–Current Status - PMC This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12415766/

Subclinical Brain Lesions in Magnetic Resonance Imaging ... PFO, patent foramen ovale; DWI, diffusion-weighted imaging. Of 424 patients, 246 (58%) had DWI lesion. Among them, 16.3% had single lesion ...

9. karger.com karger.com/ced/article/48/1-2/45/77163/Diffusion-Weighted-Imaging-Patterns-According-to

Diffusion-Weighted Imaging Patterns According to the ... Background: Although patent foramen ovale (PFO) is considered to be the main cause of cryptogenic stroke, it is difficult to define “true” ...