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

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 Imaging for Cardiac Vasculopathy After Heart Transplant?

PET imaging, specifically PET/CT scans, have shown high accuracy in diagnosing cardiac allograft vasculopathy (CAV) and are recommended for evaluating heart transplant patients. This imaging method can effectively assess blood flow in the heart, helping to identify issues without invasive procedures. ^{1 2 3 4 5}

Is PET imaging safe for humans?

PET imaging, used as a noninvasive alternative to invasive coronary angiography (ICA) for heart transplant patients, is generally considered safe. While the research does not specifically address safety concerns, PET/CT scans are widely used in medical practice, suggesting a favorable safety profile. ^{2 3 5 6 7}

How does PET imaging differ from other treatments for cardiac vasculopathy after heart transplant?

PET imaging is unique because it provides a noninvasive way to assess both the large and small blood vessels in the heart after a transplant, offering high diagnostic accuracy for detecting cardiac vasculopathy. Unlike traditional invasive coronary angiography, PET imaging can evaluate myocardial blood flow and reserve, helping to stratify patient risk without the need for invasive procedures. ^{1 3 8 9 10}

What is the purpose of this trial?

Cardiac allograft vasculopathy (CAV) is a common complication affecting heart transplant patients. This condition causes narrowing of the heart arteries leading to graft dysfunction. Surveillance for CAV is vital; however an ideal approach has not been established. The goal of this study is to assess whether noninvasive positron emission tomography (PET) based surveillance is non-inferior to invasive coronary angiography (ICA) surveillance.

Research Team

Sharon Chih

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

PET Assessment of Cardiac Allograft Vasculopathy. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

Usefulness of dual-source computed tomography for the evaluation of coronary arteries in heart transplant recipients. [2019]

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

Negative Predictive Value and Prognostic Associations of Rb-82 PET/CT with Myocardial Blood Flow in CAV. [2023]

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

Multislice computed tomography to rule out coronary allograft vasculopathy in heart transplant patients. [2016]

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

Coronary CTA for Surveillance of Cardiac Allograft Vasculopathy. [2023]

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

Serial intracoronary ultrasound in children: feasibility, reproducibility, limitations, and safety. [2019]

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

Cardiac allograft vasculopathy after heart transplantation: electrocardiographically gated cardiac CT angiography for assessment. [2022]

8. Japan 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. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

[Early diagnosis and management of cardiac allograft vasculopathy: is it time for a standardized approach?] [2021]

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

Cardiac CT of the transplanted heart: indications, technique, appearance, and complications. [2016]