To assess whether vutrisiran treatment was associated with changes in cardiac structure, function, and amyloid burden on serial cardiovascular magnetic resonance (CMR) imaging among HELIOS-B participants.
Approach:
Study design: Post hoc analysis of serial CMR data from UK National Amyloidosis Centre participants in the randomized HELIOS-B trial.
Participants and imaging: Baseline CMR was available for 43 participants: 21 assigned to vutrisiran and 22 to placebo. Follow-up CMR was available for 39 at year 1, 26 at year 2, and 17 at year 3.
Analysis: Mixed models using all available repeated measurements estimated treatment-group differences; sensitivity analyses used last observation carried forward.
Key Findings:
Compared with placebo, vutrisiran was associated with higher left ventricular ejection fraction (least-squares mean difference, 19.18%; 95% CI, 11.76%-26.60%; P<.001) and right ventricular ejection fraction (16.28%; 95% CI, 9.58%-22.97%; P<.001).
Vutrisiran was associated with higher left and right ventricular stroke volumes, with between-group differences of 27.82 mL (P<.001) and 23.69 mL (P=.003), respectively.
Vutrisiran was associated with lower left ventricular mass (difference, −23.58 g; P=.002) and extracellular volume (ECV; difference, −6.56%; P<.001).
At year 3, amyloid regression was observed in 2 of 9 vutrisiran recipients and none of 8 placebo recipients; progression was observed in 1 of 9 and 5 of 8, respectively.
Among year-3 CMR completers, mean ECV changed by −0.10% (SD, 4.72%) with vutrisiran and +7.86% (SD, 5.67%) with placebo.
Sensitivity analyses supported favorable changes in left ventricular stroke volume and ejection fraction; the ECV treatment effect was attenuated.
Interpretation:
In this post hoc CMR analysis of a small UK HELIOS-B subgroup, vutrisiran treatment was associated with favorable changes in ventricular function, left ventricular mass, and ECV compared with placebo.
Limitations:
The analysis included only 43 participants at baseline, with 17 completing CMR at year 3.
The analysis was post hoc and based on a single UK trial subgroup.
Follow-up imaging was unavailable for some participants; deaths and other reasons contributed to attrition.
by Yousuf Razvi, Awais Sheikh, Rishi K. Patel, Anouk Achten, Josephine Mansell, Ana Martinez-Naharro, Lucia Venneri, Philip N. Hawkins, James Moon, John Vest, Sameer Bansilal, Satish Eraly, Emre Aldinc, Brian L. Claggett, Scott D. Solomon, Julian D. Gillmore, Marianna Fontana
