Left Atrial Strain Indicates Worse ATTR-CM Prognosis, but Attenuable With Vutrisiran

Left atrial (LA) dysfunction among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) indicates a worse prognosis; however, treatment with vutrisiran can attenuate the progression of atrial myopathy in this population.1

ATTR-CM is increasingly becoming a core cause of heart failure, related to the deposition of misfolded transthyretin as amyloid fibrils in the heart. LA amyloid infiltration and LA remodeling have been shown to contribute to LA dysfunction in patients diagnosed with ATTR-CM. LA strain, already an important indicator of several disease states, may also be reflective of disease burden in this population.1

“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,” Karola Jering, MD, a cardiovascular research fellow at Brigham and Women’s Hospital, and colleagues wrote. “However, data on its prognostic importance in patients with ATTR-CM and response to disease-modifying therapy remain limited.”1

To this end, Jering and colleagues conducted a secondary analysis of the HELIOS-B trial. HELIOS-B was a randomized, double-blind, placebo-controlled, multicenter phase 3 study evaluating the efficacy and safety of vutrisiran in patients with ATTR-CM. Patients were eligible for inclusion if they had a documented diagnosis of ATTR-CM, classified as either hereditary or wild-type ATTR, and medical history of heart failure with ≥1 prior hospitalization or clinical evidence. Patients were excluded if they had known primary amyloidosis, New York Heart Association Class IV heart failure, a polyneuropathy disability, or other non-TTR cardiomyopathy, among other criteria.2

A total of 655 patients were enrolled in the trial and were randomly assigned to receive either vutrisiran 25 mg (n = 326) or placebo (n = 329) every 12 weeks for ≤36 months. The primary endpoint was a composite of all-cause mortality and recurrent cardiovascular events, defined as hospitalizations or urgent visits from heart failure. Secondary endpoints included death from any cause, change from baseline in the 6-minute walk test, and change from baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score.3

Ultimately, vutrisiran treatment led to a lower risk of death from any cause and recurrent cardiovascular events compared to placebo – 125 patients in the vutrisiran group and 159 in the placebo group had ≥1 primary endpoint event. Additionally, vutrisiran recipients had a smaller decline in distance covered in the 6-minute walk test.2

In the present secondary analysis of the HELIOS-B trial, Jering and colleagues analyzed the 644 patients with measurable LA strain. The study indicated that patients with worse LA reservoir (LASr) had more advanced disease, more left ventricular systolic and diastolic dysfunction, and more atrial fibrillation. Additionally, LASr and LA contractile strain (LASct) were both independently associated with ACM and recurrent cardiovascular events (LASr: 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 hospitalization (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, 1.3; 95% CI, 1.03-1.63; P = .03: LASct: HR, 2.02; 95% CI, 1.38-2.96; P <.001).1

Ultimately, Jering and colleagues determined that LA dysfunction is not only common among patients with ATTR-CM, but also consistently portends worse prognoses. Vutrisiran’s beneficial effect on other measures of cardiac structure also extended to this population, attenuating worsening LA strain at 30 months.1

“These findings support the importance of LA function in the pathophysiology of ATTR-CM and the ability of silencer therapy with vutrisiran to attenuate worsening of atrial myopathy in amyloid heart disease,” Jering and colleagues wrote.1

References

1. Jering KS, Manafi A, Claggett BL, et al. Left atrial structure and function, clinical outcomes, and efficacy of Vutrisiran in transthyretin amyloidosis with cardiomyopathy. JAMA Cardiology. August 19, 2026. Accessed August 20, 2026. doi:10.1001/jamacardio.2026.2992

2. Alnylam Pharmaceuticals. HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy. ClinicalTrials.gov Identifier: NCT04153149. Updated January 12, 2026. Accessed August 20, 2026. https://clinicaltrials.gov/study/NCT04153149?cond=NCT04153149&viewType=Card&rank=1

3. Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. New England Journal of Medicine. 2025;392(1):33-44. doi:10.1056/nejmoa2409134