Abstract Body (Do not enter title and authors here): Hypothesis&Purpose: Concomitant aortic stenosis (AS) and transthyretin-association cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure. Aortic valve replacement (AVR) improves prognosis, but the efficacy of ATTR-specific medication remains unclear in this population. We aimed to investigate the prognostic implications of ATTR-specific medication in patients with dual AS-CA.

Study Design&Methods: Multi-center, international, transatlantic registry of patients with a concomitant pathology of significant AS (moderate/severe) and ATTR-CA (ClinicalTrials.gov: NCT06129331). AS severity was diagnosed by transthoracic echo and ATTR-CA by myocardial uptake on bone scintigraphy and/or endomyocardial biopsy in the absence of monoclonal protein.

Sample Size: 226 patients.

Population: Patients with dual AS-CA identified in 16 centers across 9 countries. A control cohort of confirmed lone AS receiving AVR matched for EuroSCORE-II was utilized for outcome comparison.

Interventions: ATTR-specific medication and AVR.

Power Calculations: We estimated higher event rates and divergence compared to the ATTR-ACT trial (advanced age, longer follow-up) at 38% for the ATTR-specific treatment and 60% for the non-treatment group (hazard ratio 63% vs 68% in ATTR-ACT). The estimated group size ratio (treatment vs no treatment) was 1:2 yielding a population size of 201 patients to detect differences in survival at 80% power and bilateral significance of α=0.05.

End Points: All-cause mortality, heart failure hospitalization (HHF).

Outcome: Of 226 patients with dual pathology (85±6 years, 80% male), AS was severe in 196 (87%), and moderate in 30 (13%). Valve treatment strategies were transcatheter/surgical AVR in 71%/4%, balloon angioplasty in 1%, and conservative management in 24%. 69 patients (31%) received ATTR-specific medication (99% tafamidis).
After 3.6±1.7 years, 112 (50%) had died and 58 (26%) experienced HHF. ATTR-specific medication was independently associated with improved survival (adjusted HR 0.42 [95%CI 0.24-0.72]), but not time to first HHF. AVR improved survival in the overall (HR 0.63 [0.40- 0.99]) and severe AS cohort (HR 0.42 [0.25-0.72]). Patients who received both ATTR-specific medication and AVR had the most favorable survival, comparable to a control cohort with lone AS undergoing AVR (log-rank, p=0.18).
In conclusion, ATTR-specific treatment and AVR both result in significant survival benefit in dual AS and ATTR-CA.