Integrating echocardiographic parameters into prognostic assessment of wild-type transthyretin amyloid cardiomyopathy

Background Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive infiltrative cardiomyopathy associated with high mortality. While staging systems incorporating biomarkers such as NT-pro-B-type natriuretic peptide (NTproBNP) and estimated glomerular filtration rate (eGFR) have been proposed to stratify risk, echocardiographic assessment may offer additional prognostic insight. Objective To evaluate the prognostic significance of echocardiographic parameters in predicting all-cause mortality in patients with wtATTR-CM. Methods In this retrospective, single-center study, patients diagnosed with wtATTR-CM between 2014 and 2024 were included. The primary outcome was all-cause mortality. Baseline clinical, biomarker (NT-proBNP, eGFR), and echocardiographic data were analyzed. Comparisons were made between patients who died during follow-up and those who survived. Multivariable Cox regression was used to identify independent echocardiographic predictors of mortality. Results A total of 111 patients were analyzed (74% male, mean age 81 ± 5 years), with a median follow-up of 31 months (IQR 16–39). During follow-up, 46 patients (41%) died. Patients who died had a higher prevalence of moderate or severe aortic stenosis (59% vs. 37.5%, p=0.031), increased interventricular septal thickness (19.0 ± 3.6 mm vs. 17.7 ± 3.1 mm, p=0.041), and elevated average E/e′ (18.2 ± 4.4 vs. 13.5 ± 6.2, p<0.001). They also exhibited more impaired myocardial function: - Right ventricular global longitudinal strain (RV GLS): –10.4 ± 4.3% vs. –12.7 ± 4.6%, p=0.010 - TAPSE: 16.2 ± 4.6 mm vs. 18.4 ± 4.5 mm, p=0.016 - Left ventricular GLS: –10.2 ± 4.1% vs. –11.8 ± 3.6%, p=0.034 - Peak atrial longitudinal strain (PALS): 7.8 ± 5.1% vs. 11.5 ± 6.2%, p=0.002 - Left atrial total emptying fraction (LATEF): 24.3 ± 12.3% vs. 34.0 ± 14.4%, p<0.001 In multivariate analysis adjusting for NT-proBNP and eGFR, both average E/e′ (hazard ratio [HR] 1.17; 95% CI 1.04–1.33; p=0.013) and RV GLS (HR 0.82; 95% CI 0.67–0.99; p=0.045) remained independent predictors of mortality. Conclusion Echocardiographic indices reflecting diastolic dysfunction (E/e′) and right ventricular systolic performance (RV GLS) independently predict mortality in patients with wtATTR-CM, beyond established biomarkers. Incorporating these parameters into current risk stratification models may improve prognostic accuracy and inform clinical decision-making.