NCT03812172

Screening for Cardiac Amyloidosis With Nuclear Imaging for Minority Populations

Screening for Cardiac Amyloidosis With Nuclear Cardiology for Minority Populations

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 646 (actual)
• Sponsor: Mathew S. Maurer, MD · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2019-05-15
• Primary completion: 2024-06-12
• Completion: 2024-12-13
• First posted: 2019-01-23
• Last updated: 2025-11-19
• Results posted: 2025-11-19

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study