Vutrisiran Treatment and Changes in Cardiac Parameters and Amyloid Burden Assessed by Cardiovascular MRI

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Importance: Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by extracellular myocardial ATTR amyloid infiltration. Vutrisiran, an RNA interference therapeutic that suppresses hepatic TTR production, met its primary end point in the HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) trial. Multiparametric cardiovascular magnetic resonance (CMR) imaging provides high-fidelity structural and functional assessment, including tissue characterization metrics, namely extracellular volume (ECV) mapping, that can track cardiac amyloid load. Objective: To analyze the association between treatment with vutrisiran and changes in cardiac structure, function, and amyloid burden by CMR imaging. Design, Setting, and Participants: This was a retrospective post hoc analysis of CMR data from participants in the UK HELIOS-B trial. This was a single-center study conducted at the UK National Amyloidosis Centre (NAC). The study population comprised participants from the HELIOS-B trial at the NAC who underwent CMR imaging at baseline and 1-, 2-, and 3-year time points as part of routine clinical care. Study data were analyzed March to April 2025. Exposure: CMR imaging during the HELIOS-B trial between April 2020 and August 2024. Main Outcomes and Measures: CMR parameters of cardiac structure, volumetrics, function, and amyloid burden were assessed. Amyloid regression and progression were defined as absolute reductions and increases in ECV of 5% or greater, respectively. Analysis was blinded to treatment allocation. Changes in CMR parameters between baseline and follow-up were evaluated; a mixed-model analysis was used to assess treatment effect. Sensitivity analyses were conducted using the last observation carried forward. Results: A total of 43 patients (mean [SD] age, 75.0 [5.7] years, 41 male [95.3%]) underwent baseline CMR imaging (21 [48.8%] received vutrisiran; 22 [51.2%] received placebo). Thirty-nine patients (21 received vutrisiran, 18 received placebo), 26 (14 received vutrisiran, 12 received placebo), and 17 (9 received vutrisiran, 8 received placebo) underwent 1-, 2-, and 3-year CMR imaging, respectively. Baseline parameters were comparable between groups. No patients received background tafamidis. Treatment with vutrisiran was associated with statistically significant and directionally favorable changes in biventricular ejection fractions (left ventricular ejection fraction least-squares mean difference, 19.18%; 95% CI, 11.76%-26.60%; P < .001; right ventricular ejection fraction, 16.28%; 95% CI, 9.58%-22.97%; P < .001) and stroke volumes (left ventricular stroke volume, 27.82 mL; 95% CI, 13.40-42.23 mL; P < .001; right ventricular stroke volume, 23.69 mL; 95% CI, 8.06-39.32 mL; P = .003), as well as reductions in left ventricular mass (-23.58 g; 95% CI, -38.78 to -8.39 g; P = .002) and ECV (-6.56%; 95% CI, -10.10% to -3.01%; P < .001). At 36 months, amyloid regression was observed in 2 of 9 patients (22%) taking vutrisiran, and no patients receiving placebo experienced regression. Conversely, 5 of 8 patients (63%) receiving placebo demonstrated progression vs 1 of 9 patients (11%) taking vutrisiran. Conclusions and Relevance: Results of this selected ATTR-CM cohort study show that treatment with vutrisiran was associated with favorable changes in parameters relating to cardiac structure, function, and amyloid burden.

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