PET/CT Imaging in Carriers of TTR Mutations

This will be a cross-sectional cohort study of 50 carriers of pathogenic TTR alleles without HF; 10-race matched non-carrier controls; and 20 patients with ATTR-CA. Participants will undergo standardized, PET/CT direct amyloid imaging assessments with I-124E to test the hypothesis that carriers of pathogenic TTR alleles without HF will have LV%ID intermediate to non-carrier controls and patients with ATTR-CA. This will address the fundamental questions of whether and to what extent cardiac amyloid infiltration is present in carriers of pathogenic TTR alleles prior to ATTR-CA disease onset.

A. Pathogenic TTR Allele Carriers without HF

Inclusion:

• men and women ages 30-80 who are pathogenic allele TTR carriers without history of HF (this will be assessed by study personnel and defined as : 1) No history of hospitalization within the previous 12 months for management of HF; 2) Without an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) a clinical diagnosis of HF from a treating clinician)
• have already completed the protocol for NCT05489549 at UT Southwestern only

Exclusion:

• a self-reported history or clinical history of HF
• other known causes of cardiomyopathy
• history of light-chain cardiac amyloidosis
• prior type 1 myocardial infarction
• cardiac transplantation
• liver transplantation
• body weight or habitus that exceeds the site-specific PET/CT parameters
• estimated glomerular filtration rate ≤30 mL/min/1.73 m2
• inability to safely undergo PET/CT
• participating in a clinical trial for ATTR treatments or taking a fibril deleting agent
• pregnancy or breastfeeding
• patients taking heparin or heparin derivatives for anticoagulation
• allergy to potassium iodide
• known uncorrected thyroid disorder

B. Subjects with symptomatic hATTR-CA (may be supplemented with other ATTR-CA genotypes including wild-type in the occasion of slow enrollment):

Inclusion:

• men and women ages 30-80 who have symptomatic V122I hATTR-CA as determined by a history of HF (this will be assessed by study personnel and defined as : 1) history of hospitalization within the previous 12 months for management of HF; 2) an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) a clinical diagnosis of HF from a treating clinician)
• hATTR-CA previously diagnosed histologically by amyloid staining and tissue typing with immunohistochemistry or mass spectrometry or by bone scintigraphy in without abnormal M-protein
• TTR gene sequencing confirming the TTR variant
• have already completed the protocol for NCT05489549 at UT Southwestern only

Exclusion:

• other known causes of cardiomyopathy
• history of light-chain cardiac amyloidosis
• cardiac transplantation
• liver transplantation
• history of type I myocardial infarction
• body weight or habitus that exceeds the site-specific PET/CT parameters
• estimated glomerular filtration rate ≤30 mL/min/1.73 m2
• inability to safely undergo PET/CT
• participating in a clinical trial for ATTR treatments or taking a fibril deleting agent
• patients taking heparin or heparin derivatives for anticoagulation
• pregnancy or breastfeeding
• allergy to potassium iodide
• known uncorrected thyroid disorder

C. Non-carrier race-matched controls:

Inclusion:

• men and women ages 30-80 who are non-carriers without history of HF (this will be assessed by study personnel and defined as: 1) No history of hospitalization within the previous 12 months for management of HF; 2) Without an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) No clinical diagnosis of HF from a treating clinician
• have previously enrolled in the Dallas Heart Study

Exclusion:

• a self-reported history or clinical history of HF
• other known causes of cardiomyopathy
• history of light-chain cardiac amyloidosis
• prior type 1 myocardial infarction
• cardiac transplantation
• liver transplantation
• body weight or habitus that exceeds the site-specific PET/CT parameters
• estimated glomerular filtration rate ≤30 mL/min/1.73 m2
• inability to safely undergo PET/CT
• participating in a clinical trial for ATTR treatments or taking a fibril deleting agent
• patients taking heparin or heparin derivatives for anticoagulation
• pregnancy or breastfeeding
• allergy to potassium iodide
• known uncorrected thyroid disorder