Assessing Stroke Risk During Surgery for Patent Foramen Ovale

(CAPPRES Trial)

Overseen by Aleksandra Pikula, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University Health Network, Toronto

Must not be taking: Anticoagulants

Disqualifiers: Stroke risk, MRI contraindications, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a multi-centre, prospective cohort study to determine if asymptomatic PFO is a risk factor for developing perioperative overt and covert stroke in patients undergoing non-cardiac surgery.

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 data supports the idea that Assessing Stroke Risk During Surgery for Patent Foramen Ovale is an effective treatment?

The available research shows that using transcranial Doppler (TCD) and diffusion-weighted MRI (DWI) can help assess stroke risk by detecting issues like microemboli, which are tiny clots that can lead to strokes. One study highlights that TCD is effective in identifying a patent foramen ovale (PFO), which is a heart condition linked to strokes. Another study suggests that TCD can be used to detect changes in blood flow that might indicate a risk of stroke. These findings suggest that these methods are useful in assessing stroke risk during surgery for PFO, making them effective tools for this purpose. ^{1 2 3 4 5}

What safety data exists for assessing stroke risk during surgery for Patent Foramen Ovale?

The safety data for assessing stroke risk during surgery for Patent Foramen Ovale includes studies using diffusion-weighted MRI (DWI) and transcranial Doppler ultrasonography (TCD). These techniques are used to detect microembolic signals and assess stroke etiology. DWI has been shown to reveal silent cerebral ischemia after procedures like pulmonary vein isolation and aneurysmal coil embolization. TCD is used to detect micro-embolic signals during such procedures, which can be related to post-procedure silent cerebral ischemia. These imaging techniques provide valuable information on the risk of cerebral embolism and stroke in various clinical settings. ^{1 6 7 8 9}

Is the treatment using special imaging techniques like MRI and ultrasound promising for assessing stroke risk during surgery for a heart condition?

Yes, the treatment using these imaging techniques is promising because they help detect heart conditions that can lead to strokes, making it easier to assess and manage stroke risk during surgery. ^{4 5 10 11 12}

Research Team

Eric Horlick, MD

Principal Investigator

University Health Network, Peter Munk Cardiac Centre

Lusine Abrahamyan, MD, PhD

Principal Investigator

University Health Network, Theta Collaborative

Aleksandra Pikula, MD

Principal Investigator

University Heath Network, Division of Neurology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Peter Munk Cardiac Centre

Collaborator

Trials

2

Recruited

910+

Findings from Research

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 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]

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 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]

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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Diffusion weighted MRI imaging and MES detection in the assessment of stroke origin. [2007]

2. United States pubmed.ncbi.nlm.nih.gov

Patent foramen ovale and transcranial Doppler. Comparison of different procedures. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Transcranial Doppler markers of diffusion-perfusion mismatch. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. Germany pubmed.ncbi.nlm.nih.gov

[Abnormalities of interatrial septum and ischemic stroke in young people]. [2019]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Silent microembolism on diffusion-weighted MRI after coil embolization of cerebral aneurysms. [2021]

7. Poland pubmed.ncbi.nlm.nih.gov

Cerebral micro-embolization during pulmonary vein isolation: Relation to post-ablation silent cerebral ischemia. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The clinical significance of diffusion-weighted MR imaging in stroke and TIA patients. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Long-term fate of left atrial thrombi and incidence of cerebral embolism under continuous anticoagulation therapy]. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

A comparison of transesophageal echocardiography and transcranial Doppler sonography with contrast medium for detection of patent foramen ovale. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Cardiac magnetic resonance imaging and transesophageal echocardiography in patients with transcatheter closure of patent foramen ovale. [2016]

12. United States pubmed.ncbi.nlm.nih.gov

Patent foramen ovale-associated stroke repeatedly misdiagnosed as cerebral small vessel disease: A case report. [2023]