LAUSR

In the HELIOS-B randomized clinical trial, the RNA interference therapeutic agent vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). In this secondary analysis of HELIOS-B, we evaluated vutrisiran’s effects on echocardiographic measures of cardiac structure and function in patients with ATTR-CM receiving vutrisiran or placebo (n = 654, 93% men). At 30 months after treatment, as compared to the placebo group, vutrisiran treatment attenuated increases in mean left ventricular (LV) wall thickness (least squares mean difference: −0.4 mm; 95% confidence interval (CI): −0.8, 0.0; P = 0.03) and LV mass index (−10.6 g m−2; 95% CI: −18.0, −3.3; P < 0.01). Vutrisiran treatment also attenuated declines in LV ejection fraction (2.0%; 95% CI: 0.3, 3.7; P = 0.02), absolute global longitudinal strain (1.2%; 95% CI: 0.7, 1.7; P < 0.01) and LV stroke volume (4.1 ml; 95% CI: 1.7, 6.4; P < 0.01), and decreased both the average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (−2.0; 95% CI: −2.9, −1.2; P < 0.01) and the early to late diastolic transmitral flow velocities ratio (−0.3; 95% CI: −0.6, −0.0; P = 0.04), as compared to placebo. Consistent with its clinical benefits, these echocardiographic findings indicate favorable effects of vutrisiran on cardiac structure and function in patients with ATTR-CM. ClinicalTrials.gov registration: NCT04153149. In the HELIOS-B randomized trial in patients with transthyretin amyloid cardiomyopathy, treatment with the RNA interference agent vutrisiran, which targets transthyretin, led to improved echocardiographic measures of cardiac structure and function, as compared to placebo.