Outpatient Worsening Heart Failure in Patients With Transthyretin Amyloidosis With Cardiomyopathy in the HELIOS-B Trial.

Background: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by misfolded transthyretin depositing as amyloid fibrils in the heart. Because disease progression is common, practical and sensitive methods are needed to monitor patients and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral loop diuretic intensification or initiation) is simple to assess and has been shown to be prognostic of mortality in patients with ATTR-CM.

Objectives: This study aimed to assess the clinical and prognostic significance of and the effect of vutrisiran treatment on outpatient worsening HF in patients with ATTR-CM from HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy).

Methods: Associations between outpatient worsening HF and a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent HF visits), all-cause mortality, and other disease progression-related endpoints were evaluated. The impact of vutrisiran over 36 months on outpatient worsening HF and an expanded composite of all-cause mortality, recurrent CV events, and outpatient worsening HF was also assessed.

Results: Overall, 321 patients (49.1%) had ≥1 outpatient worsening HF, 245 (37.5%) had ≥1 CV event(s), and 120 (18.3%) died; 237 patients (36.2%) had no events. Patients with outpatient worsening HF had an increased risk of all-cause mortality and CV events (HR: 2.58; 95% CI: 2.04-3.27) and all-cause mortality (HR: 2.45; 95% CI: 1.70-3.52), as well as a greater deterioration in 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and a greater increase in N-terminal prohormone of B-type natriuretic peptide. In recurrent event analyses over the double-blind period, vutrisiran vs placebo reduced the rate of outpatient worsening HF (relative rate ratio: 0.66; 95% CI: 0.56-0.78). Vutrisiran also reduced the risk of the composite of all-cause mortality, CV events, and outpatient worsening HF vs placebo (HR: 0.69; 95% CI: 0.57-0.83).

Conclusions: Outpatient worsening HF was frequent in patients with ATTR-CM in HELIOS-B, was associated with increased mortality, and reduced by vutrisiran. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).