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 a standardized departmental clinical follow-up protocol 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 post-dose. The CMR analysis was conducted by at least two experienced readers, blinded to treatment allocation and clinical data.3,4

 Patient Demographics & Baseline Characteristics

A total of 43 patients from the UK National Amyloidosis Centre who participated in HELIOS-B underwent baseline CMR imaging. The baseline characteristics of patients from the UK National Amyloidosis Centre was comparable with the UK and global HELIOS-B cohorts (Table 1).3,4

Table 1. Baseline Characteristics of the CMR Cohort and All HELIOS-B Participants.3,4

Baseline CMR parameters of the patients from the UK National Amyloidosis Centre are presented in Table 2.3,4

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

Table 2. Baseline CMR Parameters of Patients from the UK National Amyloidosis Centre Enrolled in HELIOS-B.4

 CMR Results

During follow-up, 2 patients in the vutrisiran group and 6 patients in the placebo group died. An additional 15 patients (8 in the vutrisiran group; 7 in the placebo group) did not undergo repeat CMR imaging, and 3 patients (2 in the vutrisiran group; 1 in the placebo group) had cardiac devices implanted.3

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. A mixed-model analysis that accounted for repeated measures and used all available patient data was performed to assess treatment effect. Statistical significance was defined as P<0.05.  Treatment outcomes from the analysis are shown in Table 3.3

Table 3. Treatment Effect of Vutrisiran Compared with Placebo on CMR Parameters From a Mixed Model for Repeated Measures Incorporating All Available Data.3,a

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

Figure 1. Mean (±SD) LV Mass and LV Stroke Volume Over Time.3,a

ECV

At follow-up, amyloid progression was defined as an absolute increase, and amyloid regression was defined as an absolute reduction in ECV of ≥5% from baseline. All other changes were considered stable.4

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

Among patients who completed the 36-month CMR imaging, 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 Time.3,a

 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; IQR = interquartile range; KCCQ = Kansas City Cardiomyopathy Questionnaire; LAA = left atrial area; LSMD = least squares mean difference; LV = left ventricular; LVEF = left ventricular ejection fraction; MCF = myocardial contraction fraction; NAC = National Amyloidosis Centre; NT‑proBNP = N-terminal pro-brain natriuretic peptide; NYHA = New York Heart Association; 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 24 August 2026

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 RK, et al. Vutrisiran treatment and changes in cardiac parameters and amyloid burden assessed by cardiovascular MRI. JAMA Cardiol. 2026. doi:10.1001/jamacardio.2026.2812

4.  Supplement to: Razvi Y, Sheikh A, Patel RK, et al. Vutrisiran treatment and changes in cardiac parameters and amyloid burden assessed by cardiovascular MRI. JAMA Cardiol. 2026. doi:10.1001/jamacardio.2026.2812