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Left Atrial Structure and Function, Clinical Outcomes, and Efficacy of Vutrisiran in Transthyretin Amyloidosis With Cardiomyopathy
Key result
Vutrisiran attenuates worsening in left atrial reservoir strain by ~1.2% versus placebo in ATTR-CM.
- n=655
Why the study?
Left atrial dysfunction may play an important role in the pathophysiology of ATTR-CM, but its prognostic significance and the effects of vutrisiran on left atrial parameters required evaluation.
Does vutrisiran attenuate worsening of left atrial structure and function, and is left atrial dysfunction prognostic for mortality and cardiovascular events in patients with transthyretin amyloidosis with cardiomyopathy?
Study Design
Type
RCT (n=655)
Multicenter
Yes
Structured PICO
Does vutrisiran attenuate worsening of left atrial structure and function, and is left atrial dysfunction prognostic for mortality and cardiovascular events in patients with transthyretin amyloidosis with cardiomyopathy?
P
Population
655 patients with transthyretin amyloidosis with cardiomyopathy, median age 77 years and 7.5% female, followed for a median of 36 months.
I
Intervention
Vutrisiran 25 mg subcutaneously every 3 months
C
Comparator
Placebo
O
Outcome
All-cause mortality and recurrent cardiovascular eventscomposite
Left atrial dysfunction is common and highly prognostic in ATTR-CM, and silencer therapy with vutrisiran significantly attenuates the worsening of left atrial strain over time compared to placebo.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Measures of LA strain were independently associated with [amyloidosis cardiomyopathy] and recurrent CV events, CV death, and recurrent HF hospitalizations, while volumetric and Doppler-based measures of LA size and function were not.”
“In ATTR-CM, where atrial mechanics are affected by both amyloid infiltration and hemodynamic load, LA strain may reflect disease burden and severity, offering prognostic value beyond conventional risk factors.”
Implication
LA strain identifies higher-risk ATTR-CM patients; extends vutrisiran benefits to slowing atrial myopathy.
Abstract
Importance: Left atrial (LA) dysfunction may play an important role in the pathophysiology of transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and is driven by LA remodeling and amyloid infiltration. Objectives: To evaluate the prognostic significance of LA structure and function among patients with ATTR-CM and to assess the effects of vutrisiran on these parameters. Design, Setting, and Participants: Post hoc analyses were conducted of the HELIOS-B phase 3 randomized clinical trial, which enrolled patients with ATTR-CM between December 2019 and August 2021 at 87 sites in 26 countries. Median (IQR) follow-up was 36 (33-36) months. Data were analyzed from July through November 2025. Interventions: Vutrisiran (25 mg subcutaneously every 3 months) vs placebo. Main Outcomes and Measures: The primary outcome was all-cause mortality (ACM) and recurrent cardiovascular events. LA structure (LA volume index [LAVi]) and function (LA reservoir [LASr], conduit [LAScd], and contractile strain [LASct]) were assessed, including the effect of vutrisiran on these measures at 30 months. Results: A total of 655 patients were enrolled. Among 644 patients with measurable LA strain (median [IQR] age, 77 [72-80] years; 48 female patients [7.5%]; 569 (88.4%) with wild-type ATTR), mean (SD) LA strain measures were substantially below normal (LASr: 9.5% [6.0%]; LAScd: 6.9% [3.9%]; LASct: 4.2% [4.0%]). Patients with worse LASr had more advanced disease, more atrial fibrillation, and more left ventricular systolic and diastolic dysfunction. LASr and LASct were independently associated with ACM and recurrent cardiovascular events (LASr: hazard ratio [HR] per 5% worsening, 1.37; 95% CI, 1.13-1.68; P = .002; LASct: HR per 5% worsening, 1.53; 95% CI, 1.08-2.17; P = .02), recurrent heart failure hospitalizations (LASr: HR, 1.66; 95% CI, 1.22-2.25; P = .001; LASct: HR, 2.23; 95% CI. 1.46-3.71; P < .001), and incident atrial fibrillation (LASr: HR, 1.30; 95% CI, 1.03-1.63; P = .03; LASct: HR, 2.02; 95% CI, 1.38-2.96; P < .001). In contrast, LAVi was not associated with these outcomes. LA strain measures at baseline did not modify the treatment effect of vutrisiran on ACM and recurrent cardiovascular events (LASr: P value for interaction = .60; LAScd: P value for interaction = .58; LASct: P value for interaction = .47). Vutrisiran attenuated worsening in LA strain vs placebo at month 30 (LASr: +1.2%; 95% CI, +0.4% to +1.9%; LAScd: +0.8%; 95% CI, +0.3% to +1.4%; LASct: +0.8%; 95% CI, 0% to +1.6%). Conclusions and Relevance: Per the results of this secondary analysis of the HELIOS-B randomized clinical trial, LA dysfunction is common among patients with ATTR-CM and portends a worse prognosis. 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04153149.
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
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Cite This Study
Jering et al. (2026) conducted an RCT in Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=655). Vutrisiran vs. Placebo was evaluated on All-cause mortality (ACM) and recurrent cardiovascular events. Vutrisiran attenuated worsening in left atrial reservoir strain versus placebo at 30 months (+1.2%; 95% CI, +0.4% to +1.9%) in patients with transthyretin amyloidosis with cardiomyopathy.