Clinical Scorecard: Cardiac MRI Assessment of Changes in Cardiac Measures and Amyloid Burden During Vutrisiran Treatment
At a Glance
Category
Detail
Condition
Transthyretin amyloid cardiomyopathy (ATTR-CM)
Key Mechanisms
Progressive myocardial extracellular deposition of transthyretin amyloid fibrils; vutrisiran suppresses hepatic TTR synthesis and lowers circulating TTR.
Target Population
Patients with ATTR-CM enrolled in HELIOS-B; this post hoc CMR analysis included 43 UK participants.
Care Setting
Longitudinal cardiac MRI follow-up in a clinical trial cohort at the UK National Amyloidosis Centre.
Key Highlights
In mixed-model analyses, vutrisiran was associated with higher left and right ventricular ejection fractions and stroke volumes than placebo.
Vutrisiran was associated with lower left ventricular mass and extracellular volume (ECV) than placebo.
At 36 months, CMR was completed by 17 participants: 9 assigned to vutrisiran and 8 to placebo.
The mixed-model estimated between-group differences were 19.18 percentage points for left ventricular ejection fraction, 16.28 percentage points for right ventricular ejection fraction, 27.82 mL for left ventricular stroke volume, and 23.69 mL for right ventricular stroke volume; left ventricular mass was lower by 23.58 g and ECV by 6.56 percentage points with vutrisiran.
The analysis included 43 UK participants with baseline CMR; follow-up CMR availability declined over time.
Guideline-Based Recommendations
Diagnosis
The study used cardiovascular magnetic resonance, including ECV mapping, to assess cardiac structure, function, and amyloid burden.
Management
In HELIOS-B, vutrisiran was administered subcutaneously at 25 mg every 12 weeks; this imaging analysis evaluated treatment-associated changes and did not provide a separate treatment recommendation.
Monitoring & Follow-up
Participants underwent serial CMR imaging at baseline and follow-up; imaging was completed by 39 patients at year 1, 26 at year 2, and 17 at year 3.
The study assessed ventricular ejection fraction, stroke volume, left ventricular mass, and ECV.
Risks
Follow-up deaths occurred in 2 vutrisiran recipients and 6 placebo recipients; the imaging analysis was not presented as a safety assessment.
Repeat CMR was not performed in 15 patients, and cardiac devices were implanted in 3 patients; the source reports these as factors affecting follow-up imaging.
Patient & Prescribing Data
The post hoc analysis included 43 HELIOS-B participants with baseline CMR: mean age 75.0 years; 41 were male and 2 female. Twenty-one were assigned to vutrisiran and 22 to placebo.
In mixed-model analyses, vutrisiran versus placebo was associated with differences of 19.18 percentage points in left ventricular ejection fraction, 16.28 percentage points in right ventricular ejection fraction, 27.82 mL in left ventricular stroke volume, and 23.69 mL in right ventricular stroke volume. Left ventricular mass was lower by 23.58 g and ECV by 6.56 percentage points. Tafamidis was not administered to participants during the study.
Clinical Best Practices
The analysis used mixed-model analyses accounting for repeated measures and incorporating all available patient data.
Sensitivity analyses used last observation carried forward; these supported favorable changes in left ventricular stroke volume and left ventricular ejection fraction, while the ECV treatment effect was attenuated.
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
