High-performance multicenter Echocardiographic diagnostic score for Transthyretin Cardiac amyloidosis: results from the REACT-SP multicenter retrospective Cohort study

Background Early recognition of transthyretin cardiac amyloidosis (ATTR-CA) remains challenging despite advances in multimodality imaging. Objectives To identify electrocardiographic and transthoracic echocardiographic predictors of ATTR-CA and to develop a diagnostic score in a large multicenter cohort. Methods This retrospective multicenter cohort study included patients enrolled in the REACT-SP registry between February 2022 and July 2023. ATTR-CA was defined by positive bone scintigraphy (Perugini ≥2) with compatible imaging findings. Multivariable logistic regression was used to identify independent predictors. Missing data were handled using multiple imputation (fully conditional specification). Model discrimination was assessed using receiver operating characteristic (ROC) curve analysis. Results A total of 500 patients were included, with a median age of 68 (49–76) years and male predominance. Electrocardiographic abnormalities, including low voltage and pseudoinfarction patterns, were frequently observed. Multivariable analysis identified age [OR 1.031 (1.008–1.053); p = 0.007], interventricular septal thickness [OR 1.449 (1.273–1.650); p < 0.001], apical sparing [OR 4.450 (2.302–8.602); p < 0.001], and diastolic dysfunction ≥ grade II [OR 3.801 (1.979–7.299); p < 0.001] as independent predictors of ATTR-CA. The derived score demonstrated excellent discrimination, with an AUC of 0.94 (95% CI 0.93–0.95), sensitivity of 91%, and specificity of 83%. Conclusion A simple model based on age and echocardiographic parameters showed excellent diagnostic performance for ATTR-CA. These findings support the use of widely available echocardiographic measures as part of an initial diagnostic approach, although external validation is required.