PET Scans for Heart Disease Risk Assessment in Women

(HER-CROWN Trial)

Overseen By Carolyn Van Dam

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Ottawa Heart Institute Research Corporation

Disqualifiers: Male, Pregnant, CVD, Neurodegenerative, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

210 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment PET scan for heart disease risk assessment in women?

PET scans are shown to be a powerful tool for diagnosing and assessing the risk of heart disease in women, offering improved accuracy even in challenging cases and lower radiation exposure. They help in diagnosing heart issues early, which can lead to better treatment and management of heart disease in women. ^{1 2 3 4 5}

Is PET imaging safe for women?

PET imaging is generally considered safe for women, but there are concerns about radiation exposure. Techniques to reduce radiation are recommended to minimize any potential risks. ^{2 6 7 8 9}

How does PET imaging differ from other treatments for assessing heart disease risk in women?

PET imaging for heart disease risk assessment in women is unique because it offers improved diagnostic accuracy, even in the presence of breast tissue or small heart size, and uses short-lived radiopharmaceuticals to reduce radiation exposure. It also allows for the quantification of blood flow to diagnose heart issues, even when there are no obvious blockages in the arteries. ^{2 4 10 11 12}

What is the purpose of this trial?

The full HER CROWN will be a prospective cohort study to propose a novel, women-specific cardiovascular risk score/ algorithm in the prediction of hard cardiovascular outcomes (myocardial infarction, unstable angina, coronary revascularization, stroke, total and cardiovascular mortality). This future study will be the first longitudinal cohort study, to our knowledge, that is focused entirely on researching the pathophysiology and natural history of cardiovascular disease in women with known female-specific risk factors. Further, the investigators are aiming to recruit a sample that is representative of the ethnic distribution in Canada. The proposed pilot study is a feasibility study as an essential preparatory step for HER CROWN.

Research Team

Kerri-Anne Mullen, PhD

Principal Investigator

UOHI

Eligibility Criteria

This trial is for women in Ontario with a valid health card, aged 25-55, who have specific conditions like gestational diabetes, PCOS, early menopause or inflammatory disorders such as Lupus. It's also open to those who've had pre-eclampsia or breast cancer.

Inclusion Criteria

I am between 25 and 55 years old.

I am female.

Ontario resident with a valid OHIP card

Exclusion Criteria

Untreated serious mental illness (e.g., untreated psychosis)

I am male.

Currently pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vanguard Phase

Feasibility study to evaluate the full study being planned, including blood samples, questionnaires, and various cardiovascular assessments

18 months

Multiple visits for assessments and data collection

Follow-up

Participants are monitored for safety and effectiveness after the vanguard phase

6 months

Treatment Details

Interventions

• PET scan

Trial Overview The HER CROWN study is testing a new way to predict heart disease in women using their medical history and PET scans. The goal is to create a risk score that considers female-specific factors and represents Canada's ethnic diversity.

Participant Groups

Group I: Sex-Specific Risk HDP Subgroup Factor Group and Age-Matched Control Group Experimental Treatment 1 Intervention

* Blood sample * Questionnaires * Arterial stiffness assessment * Transthoracic Echocardiogram * Coronary Computed Tomography Angiography (CTA) * Cardiac Positron Emission Tomography (PET)

Group II: Sex-Specific Risk factor group and Age-Matched Control Group Active Control 1 Intervention

* Blood sample * Questionnaires * Arterial stiffness assessment

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Findings from Research

Women experience higher complication rates and in-hospital mortality after myocardial infarction compared to men, despite having a smaller overall burden of coronary artery disease (CAD).

Certain risk factors, such as diabetes, low HDL cholesterol, high triglycerides, and psychological depression, are particularly concerning for women and can lead to worse outcomes in CAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular disease in women: sex differences in presentation, risk factors, and evaluation. Polk, DM., Naqvi, TZ.[2022]

In a study of 619 patients (138 women) followed for an average of 5.7 years, abnormal myocardial perfusion identified by PET was linked to a significantly higher risk of adverse cardiovascular events in women compared to men, indicating a need for gender-specific risk assessment.

While abnormal coronary flow reserve (CFR) was a strong predictor of long-term cardiac events in men, it did not show the same predictive value in women, suggesting that current imaging strategies may need to be refined for better risk prediction in female patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in the long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography. Gebhard, C., Fiechter, M., Herzog, BA., et al.[2018]

Mortality from coronary artery disease in women decreased from nearly 500,000 in 2000 to 398,096 in 2013, indicating progress but still highlighting the need for improved awareness and management of cardiovascular diseases.

Advancements in cardiovascular imaging have enhanced the early diagnosis and management of ischemic heart disease, suggesting that personalized applications of these technologies could lead to further reductions in mortality among women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing the trajectory of ischemic heart disease in women: Role of imaging. Dorbala, S., Shaw, LJ.[2021]

Radionuclide myocardial perfusion imaging with PET is becoming increasingly important for diagnosing and assessing the risk of coronary artery disease (CAD) in women, who often remain unaware of their cardiovascular risks.

PET imaging offers several advantages for women, including improved diagnostic accuracy in the presence of breast tissue, reduced radiation exposure, and the ability to measure myocardial blood flow, which helps diagnose ischemia even without obstructive CAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of positron emission tomography in the evaluation of myocardial ischemia in women. Taqueti, VR., Dorbala, S.[2018]

Coronary artery disease (CAD) is increasingly prevalent among women, with its incidence doubling in the past decade, yet women are still diagnosed later and treated less aggressively than men.

Advancements in myocardial perfusion imaging, particularly with technetium-99m agents, have improved the detection of CAD in women, achieving sensitivity and specificity comparable to that in men, making it a reliable noninvasive follow-up test for women with heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary artery disease. The other half of the heaven. Milan, E.[2016]

In a study of 624 women undergoing NH3-PET/CT scans, 77% had normal results, and those with abnormal scans were significantly more likely to experience major adverse cardiovascular events (MACE), with 38 out of 142 abnormal scans leading to MACE compared to only 3 out of 482 normal scans.

The study found that while the pharmacological stress ECG (PxECG) results also correlated with MACE, the relationship was stronger with NH3-PET/CT outcomes, indicating that an abnormal NH3-PET/CT is a more critical predictor of cardiovascular risk than PxECG results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relation between pharmacological stress ECG, 13NH3-PET/CT outcome and the occurrence of cardiac events during follow-up in women with chest pain. van der Zant, FM., Maurits, W., Lazarenko, SV., et al.[2021]

Both SPECT and PET myocardial perfusion imaging (MPI) are effective tools for risk stratifying women with stable ischemic heart disease (SIHD), helping to identify those at higher risk for major heart events.

Incorporating coronary flow reserve (CFR) measurements with PET enhances risk detection, especially in women with nonobstructive coronary artery disease, and new imaging techniques may allow for better identification of at-risk women by combining functional and anatomical assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial perfusion imaging in women for the evaluation of stable ischemic heart disease-state-of-the-evidence and clinical recommendations. Taqueti, VR., Dorbala, S., Wolinsky, D., et al.[2023]

Traditional risk assessments for ischemic heart disease often overlook women, as they frequently have normal or nonobstructive coronary arteries despite experiencing ischemic symptoms.

Positron emission tomography (PET) imaging can measure absolute myocardial blood flow, providing insights into other mechanisms like endothelial dysfunction that contribute to ischemic heart disease in women with nonobstructive coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary microvascular dysfunction in women with nonobstructive ischemic heart disease as assessed by positron emission tomography. Campisi, R., Marengo, FD.[2020]

Cardiac CT is particularly important for women due to unique aspects of coronary heart disease (CHD), such as atypical symptoms and a higher prevalence of noncalcified plaque, which traditional risk models like the Framingham Risk Score may not adequately address.

Coronary CT angiography is effective and cost-efficient for diagnosing significant CHD in symptomatic women, but safety concerns regarding radiation exposure are being mitigated through advanced techniques to reduce radiation doses, especially to sensitive areas like the breast.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac CT in women: clinical application and considerations. Simprini, LA., Taylor, AJ.[2016]

Myocardial perfusion imaging is an effective noninvasive test for detecting coronary artery disease (CAD) in women, especially when considering breast tissue artifacts, and is preferred over radionuclide angiocardiography for this purpose.

While intravenous dipyridamole stress testing shows comparable accuracy for both genders, women experience a higher incidence of side effects, highlighting the need for more gender-specific data in cardiovascular nuclear testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gender-related imaging issues in assessment of coronary artery disease by nuclear techniques. Grover-McKay, M.[2018]

Cardiac positron emission tomography (PET) is a powerful imaging tool that enhances the diagnosis and risk assessment of ischemic heart disease, which is the leading cause of death globally.

By quantifying myocardial blood flow and myocardial flow reserve, cardiac PET offers superior characterization of coronary artery disease compared to other imaging methods, especially in cases of microvascular and balanced multivessel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on myocardial blood flow quantification by positron emission tomography. Fernandes, J., Ferreira, MJ., Leite, L.[2021]

Coronary artery disease is the leading cause of death in women, but noninvasive testing often results in high false-positive rates, creating a diagnostic challenge.

Stress echocardiography may be a more effective initial test for women suspected of coronary artery disease due to its greater specificity, potentially reducing unnecessary coronary angiographies and aligning with a sex-specific diagnostic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of coronary artery disease in women. The pitfalls of noninvasive tests. Laurienzo, JM.[2016]

References

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

Cardiovascular disease in women: sex differences in presentation, risk factors, and evaluation. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Sex differences in the long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography. [2018]

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

Changing the trajectory of ischemic heart disease in women: Role of imaging. [2021]

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

The role of positron emission tomography in the evaluation of myocardial ischemia in women. [2018]

5. Italy pubmed.ncbi.nlm.nih.gov

Coronary artery disease. The other half of the heaven. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Relation between pharmacological stress ECG, 13NH3-PET/CT outcome and the occurrence of cardiac events during follow-up in women with chest pain. [2021]

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

Myocardial perfusion imaging in women for the evaluation of stable ischemic heart disease-state-of-the-evidence and clinical recommendations. [2023]

8. China pubmed.ncbi.nlm.nih.gov

Coronary microvascular dysfunction in women with nonobstructive ischemic heart disease as assessed by positron emission tomography. [2020]

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

Cardiac CT in women: clinical application and considerations. [2016]

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

Gender-related imaging issues in assessment of coronary artery disease by nuclear techniques. [2018]

11. Spain pubmed.ncbi.nlm.nih.gov

Update on myocardial blood flow quantification by positron emission tomography. [2021]

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

Detection of coronary artery disease in women. The pitfalls of noninvasive tests. [2016]