Effect of Acoramidis on Myocardial Structure and Function in Transthyretin Amyloid Cardiomyopathy: Insights From the ATTRibute-CM Cardiac Magnetic Resonance (CMR) Substudy

ransthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure.Acoramidis, a high-affinity TTR (transthyretin) stabilizer, inhibits tetrameric TTR dissociation, which can lead to amyloid fibrils.ATTRibute-CM (a phase 3, multicenter, double-blind trial) randomized participants with ATTR-CM to receive acoramidis or placebo (2:1).It met its primary hierarchical end point of mortality, cardiovascular-related hospitalization, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk test (P<0.0001). 1 Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping has proven utility in tracking response to treatment in ATTR-CM by assessing changes in cardiac structure, function, and amyloid burden. 2 Eligible ATTRibute-CM participants were invited to enroll in the preplanned, exploratory CMR substudy (end points: change in left ventricular [LV] mass, biventricular structure and function, and myocardial tissue characterization, including ECV mapping).ATTRibute-CM was approved by the research ethics committee, and all participants provided written informed consent.After the initial CMR scan, participants underwent scans at month 12, month 24, and month 30 (M30).M30 results are reported, as treatment effects accrue progressively to match with the ATTRibute-CM efficacy results.Amyloid regression was defined as an absolute reduction in ECV ≥5%, progression as an absolute increase in ECV ≥5%, and stable if ECV change was <5%. 3 The 5% threshold is an established independent prognosticator in light chain amyloid cardiomyopathy, and its robustness and applicability in ATTR-CM are supported by emergent data.Fifty-two participants (47 male; mean age, 74.3 years) were enrolled.Eight had variant ATTR-CM (V122I=6; T60A=2); the remainder had wild-type ATTR-CM.Twenty-six of 41 acoramidis recipients and 5 of 11 receiving placebo completed M30 scans.Baseline characteristics were comparable.Mortality was higher in placebo recipients (n=4/11; 36%) versus acoramidis (n=5/41; 12%).Before M30, 8 participants (acoramidis =7/26) received cardiac device implantations and 4 discontinued (acoramidis =3; placebo =1); thus, they were excluded.Three participants underwent M30 CMR without ECV due to exclusionary renal impairment (acoramidis =1) and technical difficulties (acoramidis =1; placebo =1).