Nuclear Imaging for Cardiomyopathy

(DISSOLvE Trial)

Overseen By Ahmad Masri, MD MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 62

Duration: 120-140 weeks

4 Participants Needed

Trial Summary

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

The protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the idea that Nuclear Imaging for Cardiomyopathy is an effective treatment?

The available research shows that Nuclear Imaging using Technetium-99m pyrophosphate is effective in identifying heart issues, such as areas with poor blood flow, especially after heart surgeries like bypass. It helps doctors see how well the heart is recovering. However, the studies mainly focus on its use for heart attacks and other heart conditions, not specifically cardiomyopathy. This imaging method is useful for checking heart damage and blood flow, but the research doesn't directly show its effectiveness as a treatment for cardiomyopathy compared to other treatments. ^{1 2 3 4 5}

What safety data exists for Technetium-99m pyrophosphate imaging?

Technetium-99m pyrophosphate (Tc-99m PYP) has been used safely in various imaging procedures. In a study involving cerebrospinal fluid leak imaging, no adverse reactions were noted in 15 patients, confirming its safety when proper precautions are taken. Additionally, its use in cardiac imaging for myocardial infarction and myocardial revascularization has been reported as safe, with no specific adverse effects mentioned in the studies. ^{1 2 3 4 6}

Is the drug 99m-technetium pyrophosphate scintigraphy promising for treating cardiomyopathy?

Yes, 99m-technetium pyrophosphate scintigraphy shows promise for treating cardiomyopathy. It has been useful in detecting heart issues in various conditions, such as heart disease from chemotherapy, bacterial infections, and heart muscle inflammation. It helps doctors see heart damage and assess heart function, making it a valuable tool in managing heart conditions. ^{2 3 4 7 8}

What is the purpose of this trial?

The investigators will evaluate the change in myocardial uptake of 99m-technetium pyrophosphate (Tc-99m PYP) tracer on serial planar and SPECT imaging in patients enrolled in the CARDIO-TTRansform clinical trial (NCT04136171).

Research Team

Ahmad Masri, MD MS

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for patients with Transthyretin Amyloid Cardiomyopathy or related heart conditions who are already part of the CARDIO-TTRansform study. They must be willing to consent and undergo additional imaging tests, and have had a specific heart scan within the last year.

Inclusion Criteria

Patients have to meet the inclusion and exclusion criteria of CARDIO-TTRansform trial to be enrolled.

Patient willing to consent for the study and undergo the study procedures.

I was eligible for or enrolled in the CARDIO-TTRansform study and had specific heart scans within the last year.

Exclusion Criteria

N/A

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo baseline Tc-99m PYP imaging to assess myocardial uptake

1 week

1 visit (in-person)

Treatment

Participants receive treatment as part of the CARDIO-TTRansform trial and undergo serial imaging

120-140 weeks

Multiple visits (in-person) for imaging at baseline, week 61, and end of trial

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 99m-technetium pyrophosphate scintigraphy

Trial Overview The study is testing how well a tracer called 99m-technetium pyrophosphate shows up in heart scans over time. This will help understand changes in patients' hearts during the CARDIO-TTRansform clinical trial.

Participant Groups

Group I: Patients with transthyretin amyloid cardiomyopathy enrolled in CARDIO-TTRansform Experimental Treatment 1 Intervention

Patients will undergo serial Tc-99m PYP imaging at baseline, week 61 and end of trial

99m-technetium pyrophosphate scintigraphy is already approved in United States, European Union for the following indications:

Approved in United States as Technetium Tc-99m pyrophosphate for:

• Diagnostic imaging scans for the bones, heart, and gastrointestinal tract
• Detection of transthyretin cardiac amyloidosis

Approved in European Union as Technetium Tc-99m pyrophosphate for:

• Diagnostic imaging scans for the bones, heart, and gastrointestinal tract

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Ionis Pharmaceuticals, Inc.

Industry Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Findings from Research

Technetium 99m labeled pyrophosphate is a safe and noninvasive imaging technique that effectively identifies areas of reduced blood flow in the heart for patients with coronary artery disease.

This imaging method has shown to be useful in assessing improvements in blood supply to the heart after coronary artery bypass surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of myocardial revascularization utilizing Tc-99m pyrophosphate. Liddicoat, JE., Bekassy, SM., Johnson, PC., et al.[2015]

In a study involving 15 patients undergoing adriamycin treatment for cancer, technetium-99m pyrophosphate imaging revealed abnormal heart accumulation in several patients.

The abnormal accumulation was particularly noted in patients with poor-risk factors, such as prior radiation therapy, cyclophosphamide treatment, and existing ischemic heart disease, suggesting a potential link between these factors and heart health during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial imaging with Cc-99m pyrophosphate in patients on adriamycin treatment for neoplasia. Chacko, AK., Gordon, DH., Bennett, JM., et al.[2015]

Cardiac patients can safely undergo 99mTc-pertechnetate (99mTc04) imaging 24 hours after receiving 99mTc-stannous pyrophosphate (99mTc-PYP), allowing for effective assessment of left ventricular function.

The method utilizes residual tin from the initial injection to label red blood cells with 99mTc04, creating a vascular tracer that enhances the quality of electrocardiographically gated imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gated blood pool imaging following 99mTc stannous pyrophosphate imaging. Stokely, EM., Parkey, RW., Bonte, FJ., et al.[2006]

In a case study of a 78-year-old man with an acute myocardial infarction, technetium-99m-pyrophosphate (99mTc-PYP) imaging revealed extensive distribution in the heart, indicating significant myocardial damage.

Despite severe coronary artery disease and a total occlusion in two major arteries, the patient was treated conservatively and discharged in stable condition after 20 days, suggesting that conservative management can be effective in certain high-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial damage of the entire ventricular region in a patient with acute myocardial infarction. Kawamata, H., Kawasaki, T., Sugihara, H., et al.[2020]

In a study of 36 patients, early technetium-99m pyrophosphate scintigraphy was used to evaluate myocardial preservation after thrombolysis, revealing that strong tracer uptake indicated poorer heart function and larger damage after an acute myocardial infarction.

The findings suggest that a strongly positive scintigraphy result within 12 hours of an acute myocardial infarction may signal inadequate success in reducing heart damage through thrombolysis, highlighting its potential as a predictive tool for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The scoring system for early technetium-99m pyrophosphate scintigraphy as a method of evaluation of limiting the myocardial infarct size by thrombolysis. Kondo, M., Yuzuki, Y., Shimizu, H., et al.[2019]

In a study of 15 patients, technetium Tc-99m pyrophosphate (PYP) provided high-quality images for cerebrospinal fluid (CSF) leak imaging, confirming its effectiveness as a diagnostic tool.

No adverse reactions were reported during the imaging procedures, indicating that Tc-99m PYP is a safe alternative for CSF leak imaging following the discontinuation of previous radiopharmaceuticals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations. Ponto, JA., Graham, MM.[2016]

A 99mTc-Pyrophosphate (99mTc-PYP) myocardial scan showed positive results in a child with congenital cyanotic heart disease, indicating its potential utility in diagnosing complications like bacterial endocarditis.

This case highlights the effectiveness of 99mTc-PYP scans in identifying myocardial involvement in pediatric patients with complex heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

99mTc-pyrophosphate imaging: bacterial endocarditis. Sty, JR., Chusid, MJ.[2019]

In a case study of a patient with severe congestive cardiomyopathy due to myocardial sarcoidosis, various imaging techniques confirmed the diagnosis, including radionuclide ventriculography and scintigraphy with thallium-201 and gallium-67.

For the first time, technetium-99m pyrophosphate (TcPYP) scintigraphy was shown to be as effective as gallium and thallium scans in detecting myocardial involvement in sarcoidosis, highlighting its potential utility in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of technetium pyrophosphate99m and gallium. Forman, MB., Sandler, MP., Sacks, GA., et al.[2019]

References

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

Evaluation of myocardial revascularization utilizing Tc-99m pyrophosphate. [2015]

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

Myocardial imaging with Cc-99m pyrophosphate in patients on adriamycin treatment for neoplasia. [2015]

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

Gated blood pool imaging following 99mTc stannous pyrophosphate imaging. [2006]

4. Iran pubmed.ncbi.nlm.nih.gov

Myocardial damage of the entire ventricular region in a patient with acute myocardial infarction. [2020]

5. Japan pubmed.ncbi.nlm.nih.gov

The scoring system for early technetium-99m pyrophosphate scintigraphy as a method of evaluation of limiting the myocardial infarct size by thrombolysis. [2019]

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

Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations. [2016]

7. Germany pubmed.ncbi.nlm.nih.gov

99mTc-pyrophosphate imaging: bacterial endocarditis. [2019]

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

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of technetium pyrophosphate99m and gallium. [2019]