Identifying Subclinical Transthyretin Cardiac Amyloidosis in V142I TTR Carriers: Design, Rationale, and Methods of the VISTA (Variant Imaging of Subclinical Transthyretin Amyloidosis) Study.

backgroundApproximately 1.5 million of the 44 million individuals of African descent in the United States are carriers of the p.V142I variant in transthyretin (TTR). This is the most common cause of variant amyloid cardiomyopathy (ATTR-CM) worldwide which leads to heart failure (HF) and premature death. Despite promising new treatments, ATTR-CM is often diagnosed at an advanced stage and conventional diagnostic tools lack specificity to detect early disease. Thus, the overall objectives of the Variant Imaging of Subclinical Transthyretin Amyloidosis (VISTA) study are to determine imaging and biomarker evidence of subclinical ATTR-CM that indicates amyloid progression in p.V142I TTR carriers. METHODS AND

resultsIn a multisite nested case-control study, contrast-enhanced cardiac resonance imaging (CMRI) and amyloid-specific blood biomarker measurements will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of p.V142I TTR carriers without HF with age-, sex-, and race-matched non-carrier controls. A sub-sample of participants will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve.

conclusionsCompletion of VISTA will establish evidence of subclinical variant ATTR-CM in p.V142I TTR carriers, will change how we think about ATTR-CM, and will justify future research in screening and treatment strategies for disease prevention.