- Peak oxygen uptake held steady over 2 years with vutrisiran and fell with placebo in patients with ATTR cardiomyopathy.
- The difference was 1.6 mL/kg/min in favor of vutrisiran.
- Patients on vutrisiran also breathed more efficiently during exercise and reached a higher peak heart rate.
Transthyretin amyloid cardiomyopathy (ATTR-CM) slowly takes away patients’ ability to exercise. In the phase 3 HELIOS-B trial, vutrisiran lowered the risk of death and recurrent cardiovascular events and slowed the decline in 6-minute walk distance compared with placebo. Less is known about how treatments like vutrisiran affect the heart and lungs during exercise.
In a late-breaking presentation at the American Heart Association 2026 Scientific Sessions, Dr. Brinda Thillainathan of the National Amyloidosis Centre at the Royal Free Hospital in London presented an analysis of HELIOS-B patients (NCT04153149) treated at that center. HELIOS-B randomized 655 patients with ATTR-CM to vutrisiran 25 mg, an injection given every 3 months, or placebo. At the National Amyloidosis Centre, patients also had cardiopulmonary exercise testing (CPET) combined with a stress echocardiogram as part of routine follow-up. In this test, patients pedal a bike while their breathing, oxygen use, and heart function are measured.
The analysis included 48 patients, 25 on vutrisiran and 23 on placebo, who had a baseline test and at least one follow-up test at 1 or 2 years. None were taking other disease-modifying treatments for ATTR-CM. Median age was in the late 70s, nearly all patients were men, and most had mild symptoms.
The main finding was in peak oxygen uptake (VO2), the most oxygen the body can use at full effort. Over 2 years, peak VO2 stayed close to baseline with vutrisiran and fell with placebo, a difference of 1.6 mL/kg/min (95% CI 0.1–3.0; P=0.031). The maximum workload patients reached on the bike did not differ significantly between groups.
Vutrisiran also helped patients breathe more efficiently. The VE/VCO₂ slope, a measure of ventilatory efficiency, increased with placebo and decreased with vutrisiran (between-group difference, −6.4; 95% CI, −10.2 to −2.6; P=0.001). Patients on vutrisiran also reached a higher peak heart rate, 7.5 percentage points more of their predicted maximum (P=0.023).
The stress echocardiogram findings did not differ significantly between groups. At peak exercise, the right ventricle contracted better with vutrisiran, with a 5.7 mm difference in tricuspid annular plane systolic excursion (TAPSE) compared with placebo (95% CI 1.7–9.7; P=0.006). Measures of how well the left ventricle fills and relaxes also favored vutrisiran. Stroke volume, cardiac output, and pulmonary artery pressure did not differ between groups.
This was a small, single-center analysis done after the trial, and the investigators noted possible selection bias. By 2 years, 17 patients remained in each group, and 4 patients on placebo had died. While HELIOS-B showed that vutrisiran lowers the risk of death and cardiovascular events in ATTR-CM, the investigators see CPET imaging as a useful way to track whether therapies like it are working.