Screening for Cardiac Amyloidosis With Nuclear Imaging for Minority Populations

NCT ID: NCT03812172

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 646 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-05-15
• Study Completion Date: 2024-12-13

Brief Summary

In this study, the investigators recruited a cohort of elderly Black and Hispanic patients with heart failure to define the number of patients who have cardiac amyloidosis by utilizing highly sensitive heart imaging and blood tests. The investigators also explored differences in genetics and sex as they relate to heart failure disease progression in cardiac amyloidosis.

Detailed Description

Heart failure with preserved ejection fraction (HFpEF) disproportionately afflicts older Black and Hispanic Americans. Transthyretin cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin (TTR or prealbumin) protein and is classified by the genetics of TTR into wild-type (ATTRwt) or hereditary (hATTR or ATTRv). ATTR CA, irrespective of genotype, is an age-dependent, often unrecognized, mechanism underlying HFpEF. While hATTR CA results from point mutations that promote TTR misfolding and amyloid aggregation, factors that contribute to ATTRwt CA are not well defined. While previously thought to be untreatable, promising therapies that have been recently reported are most effective if administered early in disease course. Only a small proportion of individuals with wild-type TTR will develop ATTRwt CA, overwhelmingly reported in Caucasian males beyond age 60 years. However, as an autosomal protein, allele distribution is not sex specific. For hATTR, a substitution of isoleucine for valine (Val142Ile) is the most frequent TTR mutation in the US, observed almost exclusively in Black Americans with an allele frequency of 3.4%. But there are no data regarding the prevalence of ATTRwt CA in African Americans and no data for ATTR CA prevalence, irrespective of genotype, in the Hispanic population. One of the reasons for the knowledge deficit is the challenge of diagnosis. Endomyocardial biopsy, while nearly 100% sensitive and specific, is impractical as a screening test and genotyping alone of patients is insufficient to identify ATTR CA because wild-type patients develop disease. In this study, the investigators used a highly accurate technique for ATTR CA identification using Tc99m-pyrophosphate (PYP) imaging that avoids the need for biopsy. (Tc99m-HDP may have been used in cases of interrupted supply of PYP) Tc99m-PYP myocardial uptake can occur before echocardiographic or clinical changes, suggesting enhanced sensitivity. While studies using the technique have suggested that 10-15% of elderly hospitalized patients with heart failure may have ATTR CA, Tc99m-PYP had not been applied broadly in heart failure patients as a means to facilitate early diagnosis. The overall hypothesis is that a significant proportion of heart failure in elderly Blacks and Hispanics is caused ATTR CA. Using these non-invasive tests, the investigators will establish the prevalence of ATTR CA.

Conditions

Amyloid Cardiomyopathy, Transthyretin-Related

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Blacks/Hispanics with Heart Failure

Blacks/Hispanics with heart failure due to transthyretin cardiac amyloidosis were identified by 99mTc-PYP (or 99mTc-HDP) scintigraphy. Those with transthyretin cardiac amyloidosis were further subtyped into those with a genetic cause (ATTRv) and those with a non-genetic cause (ATTRwt - wild type transthyretin cardiac amyloidosis).

99mTc-PYP or 99m Tc-HDP

Intervention Type: DRUG

10-25 mCi of 99mTc-PYP (or 99m Tc-HDP) was administered intravenously and imaging was performed after 3 hours.

Interventions

99mTc-PYP or 99m Tc-HDP

10-25 mCi of 99mTc-PYP (or 99m Tc-HDP) was administered intravenously and imaging was performed after 3 hours.

Intervention Type: DRUG

Other Intervention Names

Technetium-99m-Pyrophosphate or Technetium-99m-HydroxyMethyleneDiphosphonate

Eligibility Criteria

Inclusion Criteria

1. Black or Hispanic of Caribbean origin.

2. Age ≥ 60 years.

3. Diagnosis of heart failure, confirmed by one of two methods:

1. Modified criteria utilized by Rich et al. which include a history of acute pulmonary edema or the occurrence of at least two of the following that improved with diuretic therapy without another identifiable cause: dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema or exertional fatigue, and

2. National Health and Nutrition Examination Survey (NHANES) congestive heart failure (CHF) criteria with a score ≥3.

4. Left ventricular septal OR inferolateral wall thickness ≥12 mm by echocardiography.

5. Left ventricular Ejection fraction >30% by echocardiography.

6. Able to understand and sign the informed consent document after the nature of the study has been fully explained.

Exclusion Criteria

1. Primary amyloidosis (AL) or secondary amyloidosis (AA).

2. Prior liver or heart transplantation.

3. Active malignancy or non-amyloid disease with expected survival of less than 1 year.

4. Heart failure, in the opinion of the investigator, primarily caused by severe left-sided valve disease. Note: if valve was repaired, subject may be considered as no longer with severe valve disease.Heart failure, in the opinion of the investigator, primarily caused by either valve disease or ischemic heart disease.

5. Heart failure, in the opinion of the investigator, primarily caused by ischemic heart disease.

6. Ventricular assist device or anticipated within the next 6 months.

7. Impairment from stroke, injury or other medical disorder that precludes participation in the study.

8. Disabling dementia or other mental or behavioral disease.

9. Enrollment in a clinical trial not approved for co-enrollment.

10. Expected use of continuous intravenous inotropic therapy in the next 6 months.

11. High risk for non-adherence as determined by screening evaluation.

12. Inability or unwillingness to comply with the study requirements.

13. Chronic kidney disease with eGFR <15 mL/min/1.73 m2 or ESRD.

14. Weight >350 lb.

15. Nursing home resident.

16. Other reason that would make the subject inappropriate for entry into this study.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: collaborator

Harlem Hospital Center

OTHER

Sponsor Role: collaborator

The Scripps Research Institute

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

Mathew S. Maurer, MD

OTHER

Sponsor Role: lead

Responsible Party

Mathew S. Maurer, MD

Arnold and Arlene Goldstein Professor of Cardiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mathew S. Maurer, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Yale University/Yale New Haven Medical Center

New Haven, Connecticut, United States

Boston Medical Center/Boston University Medical Center

Boston, Massachusetts, United States

Columbia University Irving Medical Center

New York, New York, United States

Harlem Hospital

New York, New York, United States

Countries

United States

References

Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. doi: 10.1056/NEJMoa1805689. Epub 2018 Aug 27.

Reference Type: BACKGROUND

PMID: 30145929 (View on PubMed)

Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, Pozniakoff T, Ruberg FL, Miller EJ, Berk JL, Dispenzieri A, Grogan M, Johnson G, Bokhari S, Maurer MS. Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis. JAMA Cardiol. 2016 Nov 1;1(8):880-889. doi: 10.1001/jamacardio.2016.2839.

Reference Type: BACKGROUND

PMID: 27557400 (View on PubMed)

Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun 14;133(24):2404-12. doi: 10.1161/CIRCULATIONAHA.116.021612. Epub 2016 Apr 22.

Reference Type: BACKGROUND

PMID: 27143678 (View on PubMed)

Ruberg FL, Maurer MS, Judge DP, Zeldenrust S, Skinner M, Kim AY, Falk RH, Cheung KN, Patel AR, Pano A, Packman J, Grogan DR. Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS). Am Heart J. 2012 Aug;164(2):222-228.e1. doi: 10.1016/j.ahj.2012.04.015.

Reference Type: BACKGROUND

PMID: 22877808 (View on PubMed)

Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Jun 11;73(22):2872-2891. doi: 10.1016/j.jacc.2019.04.003.

Reference Type: BACKGROUND

PMID: 31171094 (View on PubMed)

Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M, Grogan M, Kristen AV, Lousada I, Nativi-Nicolau J, Cristina Quarta C, Rapezzi C, Ruberg FL, Witteles R, Merlini G. Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis. Circ Heart Fail. 2019 Sep;12(9):e006075. doi: 10.1161/CIRCHEARTFAILURE.119.006075. Epub 2019 Sep 4.

Reference Type: BACKGROUND

PMID: 31480867 (View on PubMed)

Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, Nair AP, Nativi-Nicolau J, Ruberg FL; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation. 2020 Jul 7;142(1):e7-e22. doi: 10.1161/CIR.0000000000000792. Epub 2020 Jun 1.

Reference Type: BACKGROUND

PMID: 32476490 (View on PubMed)

Ruberg FL, Teruya S, Helmke S, Smiley DA, Fine D, Kurian D, Raiszadeh F, Prokaeva T, Spencer B, Wong S, Pandey S, Blaner WS, DeLuca A, Johnson LL, Kinkhabwala MP, Leb J, Mintz A, LaValley MP, Einstein AJ, Cohn E, Gallegos C, Murtagh G, Kelly JW, Miller EJ, Maurer MS. Transthyretin Cardiac Amyloidosis in Older Black and Hispanic Individuals With Heart Failure. JAMA Cardiol. 2025 Oct 1;10(10):1034-1043. doi: 10.1001/jamacardio.2025.2948.

Reference Type: DERIVED

PMID: 40928765 (View on PubMed)

Madhani A, Sabogal N, Massillon D, Paul LD, Rodriguez C, Fine D, Helmke S, Winburn M, Kurian D, Raiszadeh F, Teruya S, Cohn E, Einstein AJ, Miller EJ, Connors LH, Maurer MS, Ruberg FL. Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study. J Am Heart Assoc. 2023 Aug;12(15):e028973. doi: 10.1161/JAHA.122.028973. Epub 2023 Jul 24.

Reference Type: DERIVED

PMID: 37486082 (View on PubMed)

Ruberg FL, Blaner WS, Chiuzan C, Connors LH, Einstein AJ, Fine D, Helmke S, Kurian D, Pandey S, Raiszadeh F, Rodriguez C, Sabogal N, Teruya S, Winburn M, Chung WK, Cohn E, Miller EJ, Kelly JW, Maurer MS. Design and Rationale the SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study. J Am Heart Assoc. 2023 Apr 18;12(8):e028534. doi: 10.1161/JAHA.122.028534. Epub 2023 Apr 17.

Reference Type: DERIVED

PMID: 37066788 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01HL139671-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAS4054

Identifier Type: -

Identifier Source: org_study_id