Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is caused by extracellular accumulation of misfolded transthyretin, which forms amyloid fibrils in the heart, increases ventricular wall thickness and stiffness, and impairs cardiac function, potentially resulting in heart failure. In secondary analysis of the HELIOS-B clinical trial, Jering et al. assessed the echocardiographic measurements of individuals with ATTR-CM. They found that vutrisiran, an RNA interference therapeutic agents that targets transthyretin, improved diastolic function and attenuated increases in mean left ventricular (LV) wall thickness and declines in LV ejection fraction over 30 months of treatment.
The researchers divided the participants of the HELIOS-B trial into two groups: 326 individuals with ATTR-CM were randomized to receive vutrisiran, and 329 individuals to receive placebo. Baseline characteristics, including echocardiographic parameters, were similar in both groups: LV and right ventricular (RV) wall thickness and LV mass were increased, the LV cavity was nondilated, and the hearts showed diastolic dysfunction and reduced absolute global longitudinal strain and LV stroke volume despite preserved LV ejection fraction. However, the participants treated with vutrisiran showed higher levels of pro-B-type natriuretic peptide and troponin I compared with participants in the placebo group. Overall, 40% of participants in the vutrisiran group and 39% of participants in the placebo group used tafamidis at baseline, which stabilizes the correctly folded transthyretin protein and prevents its accumulation. Of the remaining participants, 22% in the vutrisiran group and 21% s in the placebo group were treated with tafamidis after a median follow-up of 17.6 months.
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