CONGRESS ABSTRACT

Introduction: Transthyretin cardiomyopathy (ATTR-CM) is associated with high morbidity and mortality. Vutrisiran, an RNA interference therapeutic, rapidly knocks down circulating levels of TTR, thus suppressing the amyloid deposition that drives disease progression. In HELIOS-B, vutrisiran decreased risks of cardiovascular (CV) events and all-cause mortality (ACM) for patients with ATTR-CM. Vutrisiran also positively impacted echocardiographic measures of left ventricular (LV) structure and function compared to placebo. Effects on systolic and diastolic function were observed as early as month 12 of treatment. We hypothesize that specific measures of LV function at baseline and changes from baseline are associated with the risk of CV events and ACM; the clinical benefits of vutrisiran are related to its impact on these measures.   Methods: HELIOS-B is a phase 3, randomized, double-blind, placebo-controlled, multicenter study. HELIOS-B randomized 655 patients with wtATTR or hATTR-CM to vutrisiran (25mg) or placebo Q3M. The primary endpoint was a composite of ACM and recurrent CV events (CV hospitalizations and urgent heart failure visits) assessed separately in the overall population and in the monotherapy population (defined as patients not on tafamidis at baseline). Patients underwent echocardiograms at baseline, months 12, 18, 24, and 30. The association of select echocardiographic parameters on outcomes, and the impact of vutrisiran on echocardiographic  parameters was assessed..   Results: At baseline (median age 77 years, 93% male, 88% wtATTR) mean LV ejection fraction was 56 ± 13%, absolute peak longitudinal strain 14 ± 3%, and mean LV wall thickness 1.8 ± 0.3 cm. Prespecified analyses evaluating the prognostic significance of echocardiographic parameters and the impact of vutrisiran will be presented.   Conclusions: Improvements in cardiac structure and function support the benefits of vutrisiran in reducing the risk of CV events and ACM compared to placebo for patients with ATTR-CM.