Cardiac transthyretin amyloidosis treatment improves outcomes after aortic valve replacement for severe stenosis.

Background And Aims
Concomitant aortic stenosis (AS) and transthyretin-associated cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of structural heart failure. Aortic valve replacement (AVR) improves prognosis in this population, but the efficacy of ATTR-specific medication remains unclear. This study aimed to investigate the prognostic implications of ATTR-specific medication in patients with dual AS-CA.Methods
This is a multicenter, international, transatlantic registry of patients with a concomitant pathology of significant AS (moderate/severe) and ATTR-CA (ClinicalTrials.gov identifier: NCT06129331). AS severity was diagnosed by transthoracic echocardiography and ATTR-CA by myocardial uptake on bone scintigraphy and/or positive endomyocardial biopsy in the absence of monoclonal proteins. Mortality [all-cause and cardiovascular (CV)] and hospitalisation for heart failure (HHF) served as clinical endpoints. Outcomes were compared with a control cohort of confirmed lone AS receiving AVR matched for EuroSCORE II.Results
Of 226 patients with dual pathology (85 ± 6 years, 80.4% male) identified in 16 centres across 10 countries, AS was severe in 196 (86.7%), and moderate in 30 (13.3%). Valve treatment strategies were transcatheter/surgical AVR in 71.7%/3.5%, balloon angioplasty in 1.3%, and conservative management in 23.5%. Seventy-three patients (32.3%) were prescribed, and 69 patients (30.5%) eventually received ATTR-specific medication (99% tafamidis) and were younger, with lower EuroSCORE II, a higher portion of moderate AS, but higher interventricular septum thickness and more severely impaired left ventricular function compared with patients without ATTR medication. After 3.6 ± 1.7 years, 112 (49.6%) had died [CV death: 89 (79.5%)] and 58 (25.7%) experienced HHF. ATTR-specific medication was independently associated with lower all-cause [weighted hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.24-0.68] and CV mortality (weighted HR 0.47, 95% CI 0.27-0.83) but not HHF. AVR improved survival in the overall (HR 0.60, 95% CI 0.39-0.93) and severe AS cohort (HR 0.42, 95% CI 0.26-0.70). Patients who received both ATTR-specific medication and AVR had the most favourable prognosis, comparable to a control cohort with lone AS undergoing AVR.Conclusions
ATTR-specific treatment and AVR both result in significant survival benefit in dual pathology AS and ATTR-CA. Results should be interpreted in the context of the non-randomized study setting and differences in patient characteristics.