Scintigraphy for Heart Failure with Amyloidosis

(TTRinHFpEF Trial)

Overseen By Abbie Macher, BS

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Dialysis, HFrEF, Negative scan, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

515 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special scan called 99mTc-pyrophosphate scintigraphy (also known as 99mTc-PYP scan or Technetium-99m pyrophosphate scintigraphy) to determine its effectiveness in detecting transthyretin amyloidosis (ATTR) in individuals with a specific type of heart failure. ATTR can sometimes cause the heart to fill improperly even when its pumping remains normal, a condition known as Heart Failure with Preserved Ejection Fraction (HFpEF). The trial aims to identify ATTR early in people with HFpEF to enable earlier treatment. It seeks patients diagnosed with HFpEF who have not yet been diagnosed with amyloidosis but suspect it might be causing their heart failure. As an unphased trial, this study provides a unique opportunity to contribute to understanding and potentially improving early detection methods for ATTR in HFpEF patients.

Do I need to stop my current medications for the trial?

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

What prior data suggests that 99mTc-pyrophosphate Scintigraphy is safe for diagnosing heart conditions?

Previous studies have shown that a special imaging test called 99mTc-pyrophosphate scintigraphy helps diagnose transthyretin amyloidosis (ATTR), a condition that can cause heart problems. Most patients tolerate this test well, with no reports of serious side effects. The test involves a small injection of a radioactive substance, allowing doctors to obtain a clearer view of the heart. Many patients have undergone this procedure safely without significant issues. Research suggests that this imaging test is generally safe for use in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of 99mTc-pyrophosphate scintigraphy for heart failure with amyloidosis because it offers a non-invasive way to detect cardiac amyloidosis, a condition that is often underdiagnosed due to its subtle symptoms. Unlike traditional methods that require invasive biopsies to confirm amyloidosis, this imaging technique allows doctors to visualize amyloid deposits in the heart without the need for surgery. This could lead to earlier and more accurate diagnosis, enabling timely and appropriate treatment for patients who might otherwise go untreated.

What evidence suggests that 99mTc-pyrophosphate Scintigraphy is effective for identifying cardiac amyloidosis in heart failure patients?

Research has shown that a special scan called 99mTc-pyrophosphate scintigraphy effectively diagnoses transthyretin amyloidosis (ATTR), which can lead to heart failure known as HFpEF. In this trial, patients aged 65 and older with HFpEF will undergo this scan to identify cardiac amyloidosis. One study found that this scan correctly identified ATTR in over 90% of cases, with 91% sensitivity and 92% specificity, indicating high accuracy in detecting the condition. The scan uses a special tracer to highlight amyloid deposits in the heart, aiding early disease detection. Early diagnosis is crucial because it allows for timely treatment and better outcomes for heart failure patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Hanna Gaggin, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older who have been diagnosed with a type of heart failure where the heart pumps normally (HFpEF). They can't join if they've had severe untreated heart valve disease, certain types of past heart failure, a negative scan for amyloid buildup in the last year, trouble lying down for scans, known amyloidosis, or are on dialysis due to advanced kidney disease.

Inclusion Criteria

I am 65 years old or older.

I have been diagnosed with heart failure with preserved ejection fraction.

Exclusion Criteria

I have never had heart failure with reduced ejection fraction, except during specific acute conditions.

I do not have severe untreated heart valve problems.

I have been diagnosed with amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study Visit

Participants undergo a single study visit for diagnostic evaluations including 99mTc-pyrophosphate SPECT scan, blood and DNA sample collection, questionnaires, 6-Minute Walk Test, ECG, and Echocardiogram

1 day

1 visit (in-person)

Follow-up

Participants' electronic health records are reviewed for up to 5 years to determine hospitalization and survival, with phone follow-ups to ascertain vital status and significant clinical events

5 years

What Are the Treatments Tested in This Trial?

Interventions

• 99mTc-pyrophosphate Scintigraphy

Trial Overview

The study is using a special imaging test called '99mTc-pyrophosphate Scintigraphy' to see how often patients with HFpEF also have ATTR amyloidosis—a condition where abnormal proteins build up in the body. The goal is to find out better ways to predict and diagnose this issue early in heart failure patients.

How Is the Trial Designed?

Group I: Patients 65 and older with Heart Failure with Preserved Ejection Fraction Experimental Treatment 1 Intervention

Patients 65 years and older presenting to Massachusetts General Hospital with a known diagnosis of HFpEF and without a diagnosis of amyloidosis in the ambulatory (outpatient) setting will undergo a 99Tc-Pyrophosphate Scan to identify Cardiac Amyloidosis

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Akcea Therapeutics

Industry Sponsor

Trials

24

Recruited

2,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Alnylam Pharmaceuticals

Industry Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Eidos Therapeutics, a BridgeBio company

Industry Sponsor

Trials

12

Recruited

2,400+

Published Research Related to This Trial

Scintigraphy using 99mTc-labeled methylene-diphosphonate (99mTc-MDP) and pyrophosphate (99mTc-PYP) is an effective noninvasive screening method for assessing organ involvement in various types of amyloidosis, including systemic AA and AL amyloidosis.

While 99mTc-MDP and 99mTc-PYP scintigraphy are useful for detecting amyloidosis, echocardiography is more sensitive for identifying cardiac involvement, highlighting the need for complementary diagnostic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soft-tissue uptake of 99mTc-diphosphonate and 99mTc-pyrophosphate in amyloidosis. Janssen, S., Piers, DA., van Rijswijk, MH., et al.[2019]

A new quantitative method for evaluating myocardial technetium-(99m)-pyrophosphate ((99m)Tc-PYP) accumulation showed significantly higher rates in patients with cardiac amyloidosis compared to those without, indicating its potential for improved diagnosis.

The study found that while both the PYP score and the PYP accumulation rate were effective in identifying cardiac amyloidosis, the quantitative accumulation rate had higher specificity, suggesting it may be a more reliable diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel method for quantitative evaluation of cardiac amyloidosis using (201)TlCl and (99m)Tc-PYP SPECT. Yamamoto, Y., Onoguchi, M., Haramoto, M., et al.[2016]

In a study of 10 patients with cardiac amyloidosis, DPD scintigraphy showed more significant associations with clinical variables, suggesting it may better reflect disease severity compared to PYP scintigraphy.

However, PYP scintigraphy was found to be more sensitive in identifying cardiac amyloidosis involvement, as indicated by a higher proportion of patients achieving elevated visual scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct comparison of diagnostic and clinical values between Tc-99 m DPD and Tc-99 m PYP scintigraphy in patients with cardiac amyloidosis. Park, YJ., Lee, J., Kim, D., et al.[2023]

In a multicenter study involving 229 participants, Tc 99m PYP cardiac imaging demonstrated high sensitivity (91%) and specificity (92%) for detecting transthyretin cardiac amyloidosis (ATTR), making it a reliable diagnostic tool.

An H/CL ratio of 1.6 or greater in Tc 99m PYP imaging was linked to significantly worse survival outcomes in patients with ATTR cardiac amyloidosis, indicating its potential prognostic value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis. Castano, A., Haq, M., Narotsky, DL., et al.[2022]

99 mTc-PYP scintigraphy demonstrated high sensitivity (88.9%) and specificity (95.0%) for diagnosing ATTR cardiac amyloidosis, making it a valuable tool in clinical practice for identifying this condition, especially in elderly patients.

The study involved 98 patients, with 29 undergoing endomyocardial biopsy, highlighting that 99 mTc-PYP scintigraphy can effectively screen for ATTR amyloidosis, which is often challenging to diagnose based solely on clinical symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of 99 mTc-Pyrophosphate Scintigraphy in Diagnosing Transthyretin Cardiac Amyloidosis in Real-World Practice. Tsutsui, Y., Kubota, T., Kato, S., et al.[2021]

Technetium-99m-labeled pyrophosphate (PYP) and DPD are effective imaging agents for diagnosing cardiac amyloidosis, capable of differentiating between light chain (AL) and transthyretin (TTR) types of the disease.

The study observed a unique pattern of increased uptake in soft tissues while sparing the organs typically most affected by cardiac amyloidosis, suggesting a distinct imaging profile for these agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unusually seen pattern of 99mTc-DPD soft tissue uptake in a patient with AL amyloidosis. Is it an amyloid type indicator in specific cases? Doumas, A., Armenis, I., Chatzoglou, V., et al.[2023]

99mTechnetium pyrophosphate (99mTc-PYP) scintigraphy is effective for diagnosing transthyretin cardiac amyloidosis, but discrepancies can occur between planar imaging and SPECT/CT fusion imaging, leading to inconclusive results.

To enhance diagnostic accuracy for ATTR cardiac amyloidosis, it is crucial to standardize the protocol and interpretation methods for 99mTc-PYP scintigraphy, particularly in distinguishing myocardial uptake from tracer accumulation in the cardiac blood pool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report of an uncommon presentation of 99mtechnetium pyrophosphate scintigraphy in transthyretin cardiac amyloidosis: A potential diagnostic pitfall, pseudo-positive or pseudo-negative? Ochi, Y., Kubo, T., Nakashima, Y., et al.[2020]

Technetium-99m-pyrophosphate myocardial scintigraphy is a sensitive and specific diagnostic tool for detecting cardiac amyloidosis, particularly in patients with congestive heart failure, as shown in a study of 20 patients with biopsy-proven primary amyloidosis.

The test demonstrated a strong correlation between increased myocardial uptake and echocardiographic abnormalities, indicating its effectiveness in identifying cardiac involvement in amyloidosis, but it was not useful for early detection in patients without echocardiographic signs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis. Falk, RH., Lee, VW., Rubinow, A., et al.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8788016/

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sciencedirect.com

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