Right Ventricular Function, Clinical Outcomes, and Effect of Vutrisiran in Transthyretin Amyloidosis with Cardiomyopathy

Importance Right ventricular (RV) dysfunction is common among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and portends worse prognosis. The effects of vutrisiran on RV function remain incompletely characterized. Objective To determine the prevalence and prognostic importance of RV dysfunction in ATTR-CM, and to evaluate the effect of vutrisiran on RV function. Design, Setting, and Participants This post hoc analysis of the HELIOS-B randomized clinical trial (December 2019 and August 2021) included participants with ATTR-CM who had adequate echocardiographic images. Median (IQR) follow-up was 36 (33-36) months. Data analysis was performed from September to December 2025. Interventions Vutrisiran, 25 mg, subcutaneously every 12 weeks vs placebo. Main Outcomes and Measures The primary outcome was a composite of all-cause mortality and recurrent cardiovascular events. RV function was assessed using tricuspid annular systolic myocardial velocity (RV S′), RV fractional area change (RV FAC), RV free wall strain (RVFWS), and RVFWS indexed to pulmonary artery systolic pressure (RVFWS/PASP). Associations with outcomes and treatment effects were evaluated. Results Among 655 participants with ATTR-CM who were randomized, 548 had adequate echocardiographic images. The mean (SD) age was 75 (7) years; 506 patients (92%) were men and 42 (8%) were women. RV dysfunction was more prevalent if defined by abnormal RVFWS (absolute RVFWS ≤20%, 85%) vs RV S′ (≤9.5cm/s, 56%) or RV FAC (≤35%, 31%). Patients in the worst RVFWS quartile (<10.8%, n = 137) had lower estimated glomerular filtration rate, lower left ventricular ejection fraction, and more advanced National Amyloidosis Centre (NAC) stage. Worse RVFWS and RVFWS/PASP were significantly associated with greater risk of all-cause mortality and recurrent cardiovascular events, independent of clinical characteristics, NAC stage, and LV global longitudinal strain. In contrast, associations of RV S′ and RV FAC with outcomes were attenuated after multivariable adjustment. At 30 months, vutrisiran stabilized RVFWS (between-group difference: 1.6%, 95% CI, 0.7 to 2.6%) and improved RVFWS/PASP compared with placebo (between-group difference: +0.08%/mm Hg; 95% CI, 0.03%/mm Hg to 0.13%/mm Hg), with no significant effect on RV FAC (−1.6%; 95% CI, −3.7% to 0.6%). Conclusions and Relevance RV dysfunction assessed by RVFWS is highly prevalent in ATTR-CM and independently predicts mortality and recurrent CV events, whereas conventional RV measures may underestimate RV dysfunction and lack independent prognostic value. This study found that, consistent with its beneficial effects on other measures of cardiac structure and function, vutrisiran stabilized RVFWS and improved RVFWS/PASP at 30 months. Trial Registration ClinicalTrials.gov Identifier: NCT04153149