research summary

Vutrisiran Slows Worsening of Left Atrial Dysfunction in ATTR-CM at 30 Months

Edited by:
Anthony Calabro, MA

Key Highlights:

  • Left atrial dysfunction was common and independently associated with adverse clinical outcomes among patients with transthyretin amyloidosis with cardiomyopathy.
  • Worsening left atrial reservoir and contractile strain was associated with all-cause mortality and recurrent cardiovascular events, recurrent heart failure hospitalizations, and incident atrial fibrillation.
  • Compared with placebo, vutrisiran reduced worsening across 3 measures of left atrial strain at 30 months.
  • Baseline left atrial strain did not modify the effect of vutrisiran on all-cause mortality and recurrent cardiovascular events.

Left atrial (LA) dysfunction was common and independently associated with adverse clinical outcomes among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), according to a secondary analysis of the HELIOS-B randomized clinical trial published in JAMA Cardiology. Compared with placebo, vutrisiran reduced worsening of LA function, as measured by LA strain, at 30 months.

The post hoc analysis used data from the phase 3 HELIOS-B trial, which enrolled 655 patients with ATTR-CM at 87 sites in 26 countries between December 2019 and August 2021. Participants received vutrisiran 25 mg subcutaneously every 3 months or placebo. Median follow-up was 36 months.

Researchers assessed LA structure using LA volume index (LAVi) and LA function using reservoir strain (LASr), conduit strain (LAScd), and contractile strain (LASct). The primary outcome was all-cause mortality and recurrent cardiovascular events. Investigators also evaluated associations with recurrent heart failure hospitalizations and incident atrial fibrillation, as well as the effect of vutrisiran on LA measurements at 30 months.

Study Findings

Among 644 patients with measurable LA strain, the median age was 77 years, 48 patients (7.5%) were female, and 569 (88.4%) had wild-type ATTR. Mean LA strain measurements were substantially below normal: 9.5% for LASr, 6.9% for LAScd, and 4.2% for LASct. Patients with worse LASr had more advanced disease, more atrial fibrillation, and greater left ventricular systolic and diastolic dysfunction.

Each 5% worsening in LASr was independently associated with all-cause mortality and recurrent cardiovascular events (hazard ratio [HR], 1.37; 95% CI, 1.13-1.68; P=.002), recurrent heart failure hospitalizations (HR, 1.66; 95% CI, 1.22-2.25; P=.001), and incident atrial fibrillation (HR, 1.30; 95% CI, 1.03-1.63; P=.03).

Each 5% worsening in LASct was also associated with all-cause mortality and recurrent cardiovascular events (HR, 1.53; 95% CI, 1.08-2.17; P=.02), recurrent heart failure hospitalizations (HR, 2.23; 95% CI, 1.46-3.71; P<.001), and incident atrial fibrillation (HR, 2.02; 95% CI, 1.38-2.96; P<.001). In contrast, LAVi was not associated with these outcomes.

At month 30, vutrisiran reduced worsening compared with placebo in LASr by 1.2% (95% CI, 0.4%-1.9%), LAScd by 0.8% (95% CI, 0.3%-1.4%), and LASct by 0.8% (95% CI, 0%-1.6%). Baseline LA strain did not modify the treatment effect of vutrisiran on all-cause mortality and recurrent cardiovascular events.

Clinical Implications

According to the study authors, LA dysfunction is prognostically important in ATTR-CM, and the findings support the role of LA function in the disease’s pathophysiology. The results also suggest that transthyretin silencing with vutrisiran can slow worsening atrial myopathy in amyloid heart disease.

Expert Commentary

“Consistent with its beneficial effects on other measures of cardiac structure and function, vutrisiran attenuated worsening in LA strain at 30 months, supporting the importance of LA function in the pathophysiology of ATTR-CM and the ability of silencer therapy with vutrisiran to attenuate worsening atrial myopathy in amyloid heart disease,” the researchers concluded.

Reference
Jering KS, Manafi A, Claggett BL, et al. Left atrial structure and function, clinical outcomes, and efficacy of vutrisiran in transthyretin amyloidosis with cardiomyopathy: a secondary analysis of the HELIOS-B randomized clinical trial. JAMA Cardiol. Published online August 19, 2026. doi:10.1001/jamacardio.2026.2992