Abstract 4368781: Effects of Vutrisiran on Measures of Cardiac Structure, Function and Amyloid Burden by Cardiovascular Magnetic Resonance from the HELIOS-B Trial

Abstract

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by extracellular deposition of amyloid in the heart. Vutrisiran, an RNA interference agent, rapidly suppresses hepatic production of TTR. The present analyses evaluate the impact of vutrisiran on cardiac structure, function and amyloid load measured by cardiovascular magnetic resonance (CMR) with extracellular volume (ECV) mapping. Purpose: To analyze the impact of vutrisiran vs placebo on cardiac structure, function and amyloid burden in HELIOS-B participants. Methods: In HELIOS-B ATTR-CM patients were randomized 1:1 to vutrisiran or placebo. The study population comprised HELIOS-B participants who underwent serial CMR assessments at the National Amyloidosis Centre as part of routine clinical care. CMRs were conducted at baseline, 1, 2, and 3-year timepoints during the HELIOS-B study. Image analysis was blinded to treatment allocation. Amyloid regression and progression were defined as an absolute reduction and increase in ECV of > 5%, respectively. Changes in CMR parameters between baseline and follow-up were evaluated, and linear regression modelling was used to determine treatment effects. Results: Forty-three patients (mean (SD) age 75.0(5.67) years, 41/43male) underwent baseline CMR (21vutrisiran, 22placebo). Thirty-nine (21 vutrisiran, 18 placebo), 26 (14 vutrisiran, 12 placebo) and 17 (9 vutrisiran, 8 placebo) patients underwent 1, 2 and 3-year CMR, respectively. No patients received background tafamidis treatment. Baseline CMR characteristics were comparable between the treatment groups. At 3 years, vutrisiran led to significant increases in left and right ventricular ejection fractions (least square mean difference LVEF+20.5%, RVEF+21.1%; both p < 0.001), stroke volumes (LVSV+27.4 mL, RVSV+25.7 mL; p = 0.005 and p = 0.026, respectively), significant reductions in LVmass (–30.8 g; p = 0.014), and cardiac amyloid load (ECV –6.7%; p = 0.009) compared to placebo. For all parameters noted above, vutrisiran led to improvements while placebo led to deterioration. Amyloid regression was observed in 22% of vutrisiran patients; no placebo patients regressed. Conversely, 63% of placebo patients demonstrated progression vs 11% for vutrisiran. Significant changes in cardiac structure and function were emergent as early as year two. Conclusion: In patients with ATTR-CM, treatment with vutrisiran was associated with improvements in cardiac structure, function and amyloid burden compared to placebo.