PET Imaging for Cardiac Vasculopathy After Heart Transplant

Recruiting at 4 trial locations

Overseen By Heather Ross

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Heart Institute Research Corporation

Disqualifiers: Severe aortic stenosis, AV block, bronchospasm, others

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

Compensation: Varies

Number of Visits: Unknown

576 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for monitoring heart artery issues in individuals who have undergone heart transplants. The researchers aim to determine if a noninvasive PET scan (a type of imaging test) is as effective as the more invasive coronary angiography (a test using dye and X-rays to view the arteries) for monitoring these issues. Individuals who had a heart transplant 2 to 10 years ago and can provide consent might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance heart transplant care.

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 prior data suggests that PET imaging is safe for cardiac vasculopathy surveillance?

Research has shown that PET scans effectively check for cardiac allograft vasculopathy (CAV), a condition affecting heart transplant patients. Studies have found that PET scans excel at ruling out this disease. However, patients with more severe CAV face some risk of negative outcomes. Specifically, the rate of negative outcomes was 6.9% for mild cases and up to 30.8% for more severe cases.

Patients generally find PET scans easy to handle, and studies support them as a non-invasive alternative to more invasive methods. While some negative outcomes are possible, they mostly relate to the severity of the condition itself, not the PET scan. This makes PET a promising and safer choice for regular heart health checks after a transplant. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PET imaging technique for cardiac vasculopathy after heart transplant because it offers a non-invasive alternative to the standard Invasive Coronary Angiography (ICA). Unlike ICA, which requires inserting a catheter into the coronary arteries, PET imaging provides detailed pictures of the heart and its blood flow without the need for invasive procedures. This could mean less risk and discomfort for patients while still providing crucial information for monitoring cardiac health. Additionally, PET imaging can detect changes in the heart's metabolism and blood flow, potentially allowing for earlier detection of issues compared to traditional methods.

What evidence suggests that PET imaging is effective for cardiac vasculopathy surveillance?

This trial will compare two methods for monitoring cardiac allograft vasculopathy (CAV) in heart transplant patients: positron emission tomography (PET) and invasive coronary angiography (ICA). Research has shown that PET is promising for monitoring CAV. Studies indicate that PET can effectively measure blood flow in the heart and help predict serious heart issues. Specifically, PET scans that assess blood flow have been linked to better predictions of future heart problems. Additionally, PET has demonstrated a good balance of correctly identifying CAV without false positives, indicating accuracy. These findings suggest PET could be a reliable and noninvasive way to monitor CAV. ^{4 6 7 8 9}

Who Is on the Research Team?

Sharon Chih

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

The MARINER trial is for adults over 18 who had a heart transplant between 2-10 years ago and can give informed consent. It's not for those with severe heart valve issues, certain heart rhythm problems without a pacemaker, bad kidney function, severe asthma-like conditions, allergies to iodine contrast used in scans, poor vein access for procedures, recent treated rejection or unstable angina/heart attack.

Inclusion Criteria

Able to provide informed consent

I had a heart transplant between 2 and 10 years ago.

Exclusion Criteria

I cannot take dipyridamole because it severely affects my breathing.

I am allergic to the dye used in heart artery tests.

I cannot have a heart artery test due to poor kidney function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization and Initial Assessment

Participants are randomized to either the PET or ICA surveillance strategy and undergo initial assessments

1-2 weeks

Surveillance

Annual CAV surveillance using either PET or ICA, with assessments of clinical outcomes

24 months

Annual visits for PET or ICA

Follow-up

Participants are monitored for safety and effectiveness after the surveillance period

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ICA
• PET

Trial Overview This study compares two ways of checking for narrowed arteries in the heart after a transplant: PET scans (a non-invasive imaging test) and ICA (an invasive procedure). The aim is to see if PET can be as good as ICA at monitoring patients without needing an invasive procedure.

How Is the Trial Designed?

Group I: Positron Emission Tomography Experimental Treatment 1 Intervention

Patients in this arm will undergo annual CAV surveillance with PET

Group II: Invasive Coronary Angiography Experimental Treatment 1 Intervention

Patients in this arm will undergo annual CAV surveillance with ICA

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

In a study of 15 heart transplant patients, 13N-ammonia PET imaging demonstrated excellent correlation with cardiovascular magnetic resonance (CMR) imaging for measuring myocardial strain, indicating its effectiveness in assessing cardiac function post-transplant.

The study found high reproducibility in strain measurements from PET, with intraclass correlation coefficients of 0.89 for circumferential strain and 0.85 for longitudinal strain, suggesting that PET can be a reliable tool for detecting cardiac allograft vasculopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

13N-ammonia positron emission tomography-derived left-ventricular strain in patients after heart transplantation validated using cardiovascular magnetic resonance feature tracking as reference. Kawakubo, M., Nagao, M., Kikuchi, N., et al.[2022]

In a study involving 88 patients for diagnostic accuracy and 401 for prognostic value, PET/CT scans with myocardial blood flow (MBF) quantification showed a high negative predictive value (97%) for moderate to severe cardiac allograft vasculopathy (CAV), indicating it can effectively rule out significant disease.

The study found that patients with PET CAV 2/3 had a significantly higher risk of adverse events (30.8% annualized event rate), suggesting that PET/CT scanning is a reliable noninvasive alternative to invasive coronary angiography (ICA) for screening CAV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Negative Predictive Value and Prognostic Associations of Rb-82 PET/CT with Myocardial Blood Flow in CAV. Abadie, BQ., Chan, N., Sharalaya, Z., et al.[2023]

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft loss after heart transplantation, making early detection crucial for effective management.

While intravascular ultrasound combined with coronary angiography is the gold standard for diagnosing rapidly progressive CAV, current guidelines recommend annual angiography for the first 5 years post-transplant, which may not be ideal for all patients due to its limitations, especially in younger patients and those with chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Early diagnosis and management of cardiac allograft vasculopathy: is it time for a standardized approach?] Moschella, MM., Turco, A., Ferlini, M., et al.[2021]

Coronary allograft vasculopathy is a significant issue for heart transplant recipients, and traditional annual coronary angiography, while useful, has limitations such as being invasive and only indirectly detecting the disease.

Electrocardiographically gated multidetector computed tomography (CT) offers a noninvasive alternative that can comprehensively evaluate both the coronary artery lumen and wall, making it a promising tool for screening and diagnosing coronary allograft vasculopathy and other post-transplant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac CT of the transplanted heart: indications, technique, appearance, and complications. Bogot, NR., Durst, R., Shaham, D., et al.[2016]

Recent advancements in coronary computed tomography angiography (CTA), such as dual-source CT and motion correction algorithms, enhance image quality and diagnostic accuracy for heart transplant recipients, especially those with elevated heart rates.

Coronary CTA is now considered a safer and potentially less costly alternative to invasive coronary angiography for monitoring cardiac allograft vasculopathy (CAV), with equivalent diagnostic accuracy and improved anatomical information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary CTA for Surveillance of Cardiac Allograft Vasculopathy. Shah, NR., Blankstein, R., Villines, T., et al.[2023]

Cardiac PET imaging is recommended for evaluating cardiac allograft vasculopathy (CAV) after heart transplantation, showing high diagnostic accuracy for assessing blood flow and flow reserve.

There is a need for multicenter prospective studies to establish optimal PET measures and diagnostic thresholds for better risk stratification of post-transplant patients with CAV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Assessment of Cardiac Allograft Vasculopathy. Chih, S., Wiefels, CC., Beanlands, RSB.[2021]

Dual-source computed tomography (DSCT) has shown high diagnostic accuracy for detecting significant coronary stenoses in heart transplant recipients, with sensitivity and specificity rates of 100% for both left and right coronary arteries.

DSCT is a safe and effective alternative to invasive coronary angiography (ICA), providing a high negative predictive value, which is crucial for excluding significant coronary issues without complications during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of dual-source computed tomography for the evaluation of coronary arteries in heart transplant recipients. Kępka, C., Sobieszczańsk-Małek, M., Pręgowski, J., et al.[2019]

Intracoronary ultrasound imaging is more sensitive than traditional angiography in detecting vessel wall disease in pediatric heart transplant patients and those with Kawasaki disease, allowing for earlier identification of potential complications.

The procedure was found to be safe, with only 11 out of 62 studies resulting in coronary vasospasm, most of which were asymptomatic and resolved quickly, indicating that intracoronary ultrasound is a feasible and effective tool for monitoring heart health in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serial intracoronary ultrasound in children: feasibility, reproducibility, limitations, and safety. Schratz, LM., Meyer, RA., Schwartz, DC.[2019]

Cardiac computed tomographic (CT) angiography without β-blockers demonstrated high diagnostic accuracy for detecting cardiac allograft vasculopathy (CAV) in heart transplant recipients, with a sensitivity of 98% and specificity of 78% for any degree of stenosis, and even higher accuracy for stenosis of 50% or more (sensitivity 96%, specificity 93%).

The study involved 138 heart transplant recipients and showed that cardiac CT angiography is a noninvasive alternative to invasive angiography for CAV detection, although the absence of coronary artery calcification alone is not sufficient to rule out CAV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac allograft vasculopathy after heart transplantation: electrocardiographically gated cardiac CT angiography for assessment. Mittal, TK., Panicker, MG., Mitchell, AG., et al.[2022]

Multislice computed tomography (MSCT) demonstrated a high negative predictive value (NPV) of 96.6% for detecting significant coronary stenosis in heart transplant patients, suggesting it can effectively rule out coronary allograft vasculopathy.

While MSCT has a lower positive predictive value (PPV) of 45.5%, it offers a less invasive alternative to coronary angiogram (CA) with reduced contrast agent exposure, especially with 256-row MSCT, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multislice computed tomography to rule out coronary allograft vasculopathy in heart transplant patients. Barthélémy, O., Toledano, D., Varnous, S., et al.[2016]

Citations

1. jnm.snmjournals.org jnm.snmjournals.org/content/66/2/264

PET/CT with Myocardial Blood Flow Assessment Is Prognostic ... This study examined the prognostic value and outcomes of CAV, assessed by 13N-ammonia PET/CT myocardial perfusion imaging in heart transplant ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCIMAGING.123.015593

Measurement of Myocardial Blood Flow With Positron ... Serial assessment of coronary flow reserve by rubidium-82 positron emission tomography predicts mortality in heart transplant recipients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6003671/

Reduced Myocardial Flow Reserve by Positron Emission ... Unfortunately, CAV is quite common following transplantation with registry data showing 30% of patients developing CAV within five years of transplantation (3).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S107135812301721X

Evaluation of cardiac allograft vasculopathy by positron ... In this review, we have summarized the available evidence to support the use of PET to establish the diagnosis of CAV and highlighted the available data about ...

5. journal.houstonmethodist.org journal.houstonmethodist.org/articles/10.14797/mdcvj.1580

Cardiac Allograft Vasculopathy: A Focus on Advances in ... Cardiac positron emission tomography with functional testing demonstrates sensitivity and specificity for the diagnosis of CAV, is prognostic for important ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8528902/

Clinical Utility of SPECT in the Heart Transplant Population Survival after heart transplant has greatly improved, with median survival now over 12 years. Cardiac allograft vasculopathy (CAV), has become a major ...

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.125.041169

18F‐FAPI‐74 Positron Emission Tomography/Computed ... Cardiac allograft vasculopathy (CAV) is the primary cause of limited long‐term survival among heart transplant recipients.

8. jacc.org jacc.org/doi/10.1016/j.jchf.2022.11.012

Negative Predictive Value and Prognostic Associations of ... An algorithm using PET/CT scanning with MBF demonstrates high a negative predictive value for CAV. PET CAV 2/3 is associated with a higher risk of adverse ...

9. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/pet-ct-with-myocardial-blood-flow-effectively-screens-for-cardiac-allograft-vasculopathy

PET/CT With Myocardial Blood Flow Effectively Screens for ... Annualized composite adverse outcome rates were 6.9%, 9.3% and 30.8% for PET CAV 0, 1 and 2/3, respectively (P < 0.001, with no significant ...