Screening for Cardiac Amyloidosis With Nuclear Imaging for Minority Populations (SCAN-MP)

Screening for Cardiac Amyloidosis With Nuclear Cardiology for Minority Populations

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.

Study Overview

• Status: Completed
• Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
• Intervention / Treatment: Drug: 99mTc-PYP or 99m Tc-HDP

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.

• Study Type: Observational
• Enrollment (Actual): 646

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University/Yale New Haven Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center/Boston University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10037
      • Harlem Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Blacks and Caribbean Hispanics with heart failure not primarily due to ischemic heart disease or valvular disease.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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).	Drug: 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.; Other Names: Technetium-99m-Pyrophosphate or Technetium-99m-HydroxyMethyleneDiphosphonate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Transthyretin Cardiac Amyloidosis (ATTR-CA) in Cohort of Caribbean Hispanics and Blacks With Heart Failure (HF)	The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive. Determination of ATTR-CA was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.	Study Participation of One Year
Age Distribution of ATTR Cardiac Amyloidosis	The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among participants ≤75 years or >75 years enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.	Study Participation of One Year
Sex Distribution of ATTR Cardiac Amyloidosis	The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among male and female participants enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.	Study Participation of One Year
Self-Identified Hispanic Ethnicity Distribution of ATTR Cardiac Amyloidosis.	The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among those self-identified as Hispanic, enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.	Study Participation of One Year
ATTR Type Distribution of Cardiac Amyloidosis	The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among those variant (v142i) and non-variant (wild-type) participants enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.	Study Participation of One Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of ATTRwt and ATTRm in Blacks and Caribbean Hispanics	Among subjects with ATTR-CA we will determine the prevalence of ATTRwt and ATTRm from the Val122Ile mutation in Blacks and Caribbean Hispanics	5 years
Sex distribution of ATTR cardiac amyloidosis	The prevalence of ATTR cardiac amyloidosis will be calculated among men and women enrolled in this study	5 years
Disease progression in ATTRwt compared to ATTRm	In the ATTR CA group alone, a composite time-to-first-event endpoint at 1-year of death, heart failure hospitalization, or 30% decline in 6-minute hall walk will be compared between ATTRwt and ATTRm subjects.	5 years
RBP4 in Urine	Retinol binding protein 4 (RBB4) will be measured in urine.	5 years

Collaborators and Investigators

• Sponsor: Mathew S. Maurer, MD
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Yale University; Boston Medical Center; The Scripps Research Institute; Harlem Hospital Center
• Investigators: Principal Investigator: Mathew S. Maurer, MD, Columbia University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): June 12, 2024
• Study Completion (Actual): December 13, 2024

Study Registration Dates

• First Submitted: January 10, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Estimated): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Heart Failure; Aging; Hispanics; Cardiac Amyloidosis; TTR mutation; Blacks
• Additional Relevant MeSH Terms: Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Heart Failure; Amyloid Neuropathies, Familial
• Other Study ID Numbers: AAAS4054; R01HL139671-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No