Design and Rationale the SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study

Abstract

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an important cause of heart failure in older individuals. Misfolding and deposition of transthyretin or prealbumin protein causes ATTR-CM in the context of a normal (wild-type) or variant TTR sequence. Variant ATTR-CM is most commonly caused by the substitution of valine for isoleucine at position 122 in transthyretin (Val122Ile or pV142I, almost exclusively observed in individuals of West African ancestry), demonstrated in 3.4% of self-identified Black individuals in the United States with an estimated 1.5 million carriers. Despite the large number of known pV142I carriers, the proportion of older Black patients with heart failure attributable to ATTR-CM remains unknown. Methods To address this knowledge gap, the SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations) study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL139671) to enroll a targeted population of self-identified, community-dwelling Black or Caribbean Hispanic patients (many of whom are of West African ancestry) >60 years of age with heart failure and identify ATTR-CM by noninvasive nuclear imaging. The principal objective of SCAN-MP is to determine the prevalence of ATTR-CM in this population. Secondary objectives will explore TTR genotype, demographics, progression of variant versus wild-type ATTR-CM, and biochemical mechanisms of transthyretin amyloid fibril formation. Conclusions The SCAN-MP study is the largest, prospective study of cardiac amyloidosis in Black and Hispanic individuals. Both wild-type and variant ATTR-CM are now treatable with the US Food and Drug-approved drug tafamidis. The insights gained from SCAN-MP are likely to improve those at risk for or afflicted with ATTR-CM. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.

Keywords: amyloidosis; cardiomyopathy; disparities; precision medicine.

Figure 1. Graphical overview of SCAN‐MP design.

Assessments are performed at baseline for all participants, and again at 6‐ and 12 months for those with a Tc‐99m‐PYP scan diagnostic of ATTR‐CM and for all with the pV142I variant irrespective of Tc‐99m‐PYP scan result. Tc‐99m‐PYP scan, TTR genotype, and genetic ancestry analysis are performed at baseline only. ATTR‐CM indicates transthyretin amyloid cardiomyopathy; ATTRv, transthyretin amyloidosis owing to any transthyretin gene variant; KCCQ, Kansas City Cardiomyopathy Questionnaire; LV, left ventricular; LVEF, left ventricular ejection fraction; RBP4, retinol binding protein–4; SCAN‐MP, Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations; SF‐12, Short Form–12; Tc‐99m‐PYP, technetium‐99m‐pyrophosphate; and TTR, transthyretin. Created with BioRender.com.