Vutrisiran: Cardiac Magnetic Resonance Imaging

Vutrisiran: Cardiac Magnetic Resonance Imaging

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 Summary

Index

Study Design – Patient Demographics & Baseline Characteristics – CMR Results – Abbreviations – References

 Study Design

HELIOS-B

HELIOS-B was a phase 3, global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of vutrisiran in patients with ATTR-CM, including both hATTR and wtATTR. Patients were randomized (1:1) to receive either vutrisiran 25 mg (n=326) or placebo (n=329) every 3 months by subcutaneous injection for up to 36 months. The primary endpoint was the composite endpoint of all-cause mortality and recurrent CV events (CV hospitalizations and urgent heart failure visits) at the end of the double-blind period in the overall population and in the monotherapy population (patients not receiving tafamidis at baseline). After the double-blind period, all remaining eligible patients were allowed to receive vutrisiran in an OLE.1

CMR Analysis

Per the study protocol, CMR was not included as an assessment as part of the HELIOS-B study.2 Patients from the UK National Amyloidosis Centre who participated in HELIOS-B and underwent serial CMR as part of their routine clinical care were retrospectively identified to analyze the association between treatment with vutrisiran and changes in cardiac structure, function, and amyloid burden. CMRs were conducted at baseline and at months 12, 24, and 36. The CMR analysis was conducted by two independent readers, blinded to treatment allocation.3 

 Patient Demographics & Baseline Characteristics

A total of 43 patients from the UK National Amyloidosis Centre who participated in HELIOS-B underwent baseline CMR. A summary of the baseline characteristics and CMR parameters is presented in Table 1.3

No patients in either treatment group received a TTR stabilizer during the study period. Of the 43 patients, 39 patients (21 patients receiving vutrisiran, 18 patients receiving placebo) completed 1‑year CMR, 26 patients (14 patients receiving vutrisiran, 12 patients receiving placebo) completed 2‑year CMR, and 17 patients (9 patients receiving vutrisiran, 8 patients receiving placebo) completed 3‑year CMR assessments.3

Table 1. Baseline Characteristics and CMR Parameters.3

 CMR Results 

The differences between the vutrisiran and placebo groups at follow-up were assessed using analysis of covariance with treatment group and baseline CMR values as covariates. The 24- and 36-month data were pooled in a mixed model analysis to assess treatment effect of vutrisiran due to reduced patient numbers at follow-up (Table 2).3

Table 2. Pooled Treatment Effect (Months 24 and 36) of Vutrisiran Compared with Placebo on CMR Parameters.3

The mean (±SD) LV stroke volume and LV mass observed in the vutrisiran and placebo groups over time are shown in Figure 1.3  

Figure 1. Mean (±SD) LV Stroke Volume and LV Mass Over 36 Months.3

ECV

In the analysis, amyloid progression and regression were defined as an absolute change of ≥5% in ECV. Changes <5% were considered stable.3

At 36 months, amyloid regression was observed in 2 out of 9 patients (22%) who received vutrisiran and no patients who received placebo. Conversely, amyloid progression was observed in 5 out of 8 patients (63%) who received placebo and 1 out of 9 patients (11%) who received vutrisiran.3

The absolute mean (±SD) change from baseline in ECV at 36 months was ‑0.10% (±4.72) in the vutrisiran group and +7.86% (±5.67) in the placebo group. The mean (±SD) ECV observed in the vutrisiran and placebo groups over time is shown in Figure 2.3

Figure 2. Mean (±SD) ECV Over 36 Months.3

 Abbreviations

ATTR-CM = transthyretin amyloidosis with cardiomyopathy; CMR = cardiac magnetic resonance; CV = cardiovascular; ECV = extracellular volume; EDV = end-diastolic volume; eGFR = estimated glomerular filtration rate; ESV =  end‑systolic volume; hATTR = hereditary transthyretin amyloidosis; KCCQ = Kansas City Cardiomyopathy Questionnaire; LAA = left atrial area; LSMD = least squares mean difference; LV = left ventricular; LVEF = left ventricular ejection fraction; LVM = left ventricular mass; NT‑proBNP = N-terminal pro-brain natriuretic peptide; OLE = open-label extension; RAA = right atrial area;  RV = right ventricular; RVEF = right ventricular ejection fraction; SD = standard deviation; SV = stroke volume; TTR = transthyretin; wtATTR = wild-type transthyretin amyloidosis.

Updated 20 November 2025

References

1.  Fontana M, Berk JL, Gillmore JD, et al.  Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med. 2025;392(1):33-44. doi:10.1056/NEJMoa2409134

2.  Protocol for: Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med. 2025;392(1):33-44. doi:10.1056/NEJMoa2409134

3.  Razvi Y, Sheikh A, Patel R, et al. Effects of vutrisiran on measures of cardiac structure, function and amyloid burden by cardiovascular magnetic resonance from the HELIOS-B trial. Presented at: American Heart Association (AHA) Annual Scientific Sessions; November 7-10, 2025; New Orleans, LA, USA.