Research Summary

Vutrisiran Stabilizes Right Ventricular Strain in ATTR-CM

Edited by:
Brian McCurdy

Key Highlights

  • Right ventricular dysfunction was identified in 85% of participants using free wall strain, compared with 56% using systolic myocardial velocity and 31% using fractional area change.
  • Worse right ventricular free wall strain independently predicted mortality and recurrent cardiovascular events.
  • Vutrisiran stabilized free wall strain and improved strain indexed to pulmonary artery systolic pressure, without a significant effect on fractional area change.

Right ventricular (RV) dysfunction assessed by free wall strain was highly prevalent and independently associated with adverse outcomes in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), according to a secondary analysis published in JAMA Cardiology. Vutrisiran stabilized this measure compared with placebo over 30 months.

The post hoc analysis of the HELIOS-B randomized clinical trial included 548 of 655 randomized participants who had adequate echocardiographic images. Mean age was 75 years, and 92% were men. Participants received vutrisiran, 25 mg subcutaneously every 12 weeks, or placebo. Median follow-up was 36 months.

Investigators evaluated RV function 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). They examined associations with the primary composite outcome of all-cause mortality and recurrent cardiovascular events, as well as treatment effects on RV function.

Study Findings

The prevalence of RV dysfunction varied by measure: 85% met the abnormal absolute RVFWS threshold of ≤20%, compared with 56% for RV S′ ≤9.5 cm/s and 31% for RV FAC ≤35%. Participants in the worst RVFWS quartile—below 10.8%, comprising 137 patients—had lower estimated glomerular filtration rate, lower left ventricular ejection fraction, and more advanced National Amyloidosis Centre stage. Worse RVFWS and RVFWS/PASP remained significantly associated with mortality and recurrent cardiovascular events after adjustment for clinical characteristics, disease stage, and left ventricular global longitudinal strain. Associations involving RV S′ and RV FAC weakened after adjustment.

At 30 months, vutrisiran stabilized RVFWS versus placebo, with a 1.6-percentage-point difference (95% CI, 0.7-2.6). RVFWS/PASP also improved, with a difference of 0.08%/mm Hg (95% CI, 0.03-0.13). The between-group difference in RV FAC was not significant: −1.6 percentage points (95% CI, −3.7 to 0.6). These findings reflect the echocardiographic and clinical associations reported in this analysis.

Clinical Implications

According to the authors, conventional RV measures may underestimate RV dysfunction and lack independent prognostic value in ATTR-CM. They interpreted the stabilization of RVFWS and improvement in RVFWS/PASP with vutrisiran as consistent with its beneficial effects on other measures of cardiac structure and function.

Expert Commentary

“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,” the researchers concluded.

Reference

Jering KS, Manafi A, Claggett BL, et al. Right ventricular function, clinical outcomes, and effect of vutrisiran in transthyretin amyloidosis with cardiomyopathy: secondary analysis of the HELIOS-B randomized clinical trial. JAMA Cardiol. 2026;11(10):961-970. doi:10.1001/jamacardio.2026.3390