In patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), vutrisiran attenuated worsening in left atrial (LA) strain at 30 months, according to a secondary analysis of the HELIOS-B trial recently published in JAMA Cardiology.

Karola S. Jering, MD; Scott D. Solomon, MD, FACC; et al., included 655 patients and assessed several measures of LA structure and function, including LA volume index, LA reservoir, LA conduit and LA contractile strain. Patients were randomized to either vutrisiran 25 mg taken subcutaneously every three months or placebo, and effect on LA strain was evaluated at 30 months.

Overall, 644 patients had measurable LA strain. Among these patients, mean LA measures analyzed were substantially below normal. The treatment effect of vutrisiran on all-cause mortality and recurrent cardiovascular events was not impacted by baseline LA strain (p value for interaction 0.60 for LA reservoir; 0.58 for LA conduit; 0.47 for LA contractile strain). When compared with placebo, vutrisiran attenuated worsening in LA strain at 30 months (LA reservoir: +1.2%; 95% CI, +0.4% to 1.9%; LA conduit: +0.8%; 95% CI, +0.3% to +1.4%; LA contractile strain: +0.8%; 95% CI, 0% to +1.6%).

Patients with worse LA reservoir were more likely to have advanced disease, atrial fibrillation (AFib) and left ventricular systolic and diastolic dysfunction. Additionally, both LA reservoir and LA contractile strain were independently associated with all-cause mortality and recurrent cardiovascular events, recurrent heart failure hospitalizations and incident AFib.

"In this post hoc analysis of HELIOS-B, even small differences in LA strain were associated with meaningful differences in clinical outcomes in a well-treated cohort of patients with ATTR-CM," write the authors. "Accordingly, preservation of LA function may represent a clinically relevant effect of vutrisiran, particularly in the context of the progressive nature of ATTR-CM."