Screening for Cardiac Amyloidosis With Nuclear Imaging for Minority Populations

Screening for Cardiac Amyloidosis With Nuclear Cardiology for Minority Populations

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03812172

Acronym

SCAN-MP

Enrollment

646

Registered

2019-01-23

Start date

2019-05-15

Completion date

2024-12-13

Last updated

2025-11-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Amyloid Cardiomyopathy, Transthyretin-Related

Keywords

Heart Failure, Cardiac Amyloidosis, TTR mutation, Blacks, Hispanics, Aging

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.

Interventions

DRUG99mTc-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.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Prevalence of Transthyretin Cardiac Amyloidosis (ATTR-CA) in Cohort of Caribbean Hispanics and Blacks With Heart Failure (HF)	Study Participation of One Year	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.
Age Distribution of ATTR Cardiac Amyloidosis	Study Participation of One Year	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.
Sex Distribution of ATTR Cardiac Amyloidosis	Study Participation of One Year	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.
Self-Identified Hispanic Ethnicity Distribution of ATTR Cardiac Amyloidosis.	Study Participation of One Year	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.
ATTR Type Distribution of Cardiac Amyloidosis	Study Participation of One Year	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.

Countries

United States

Participant flow

Recruitment details

Black and Hispanic Caribbean patients with heart failure were recruited from North Manhattan (NYP West and Harlem Hospitals), Boston and New Haven via academic research facilities at Columbia University Irving Medical Center, Boston Medical Center and Yale/New Haven Health Center from 5-19-2019 until 6-12-2024

Participants by arm

Arm	Count
Self-Identified as Black, Subjects With Heart Failure ATTR-CA prevalence among subjects with heart failure self-identified as Black within predefined categories, (i.e., overall, men, women, Hispanic ethnicity age ≤75 and age \>75) Transthyretin cardiac amyloidosis status was determined by 99mTc-PYP (or 99mTc-HDP) scintigraphy. Those with transthyretin cardiac amyloidosis were further subtyped into those with a genetic cause (ATTRv - variant transthyretin cardiac amyloidosis) and those with a non-genetic cause (ATTRwt - wild-type transthyretin cardiac amyloidosis).	550
Self-identified as Non-Black, Subjects With Heart Failure ATTR-CA prevalence among subjects with heart failure not self-identified as Black within predefined categories, (i.e., overall, men, women, Hispanic ethnicity age ≤75 and age \>75) Transthyretin cardiac amyloidosis status was determined by 99mTc-PYP (or 99mTc-HDP) scintigraphy. Those with transthyretin cardiac amyloidosis were further subtyped into those with a genetic cause (ATTRv - variant transthyretin cardiac amyloidosis) and those with a non-genetic cause (ATTRwt - wild-type transthyretin cardiac amyloidosis).	96
Total	646

Baseline characteristics

Characteristic	Self-Identified as Black, Subjects With Heart Failure	Self-identified as Non-Black, Subjects With Heart Failure	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	432 Participants	80 Participants	512 Participants
Age, Categorical Between 18 and 65 years	118 Participants	16 Participants	134 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	90 Participants	96 Participants	186 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	460 Participants	0 Participants	460 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	547 Participants	0 Participants	547 Participants
Race (NIH/OMB) More than one race	3 Participants	0 Participants	3 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	83 Participants	83 Participants
Race (NIH/OMB) White	0 Participants	12 Participants	12 Participants
Sex: Female, Male Female	282 Participants	45 Participants	327 Participants
Sex: Female, Male Male	268 Participants	51 Participants	319 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	22 / 550	9 / 96
other Total, other adverse events	2 / 550	0 / 96
serious Total, serious adverse events	0 / 550	0 / 96

Outcome results

Primary

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.